PreprintPDF Available
Preprints and early-stage research may not have been peer reviewed yet.

Abstract and Figures

COVID-19 pandemic is a serious problem in the world today. The SARS-CoV-2 virus that causes COVID-19 has important proteins used for its infection and development, namely the protease and spike glycoprotein. The RBD (Receptor Binding Domain) of spike glycoprotein (RBD-S) can bind to the ACE2 (Angiotensin Converting Enzyme-2) receptor at the protease domain (PD) (PD-ACE2) of the host cell, thereby leading to a viral infection. This study aims to reveal the potential of compounds contained in Curcuma sp., Citrus sp., Alpinia galanga, and Caesalpinia sappan as anti SARS-CoV-2 through its binding to 3 protein receptors. The study was conducted by molecular docking using the MOE 2010 program (licensed from Faculty of Pharmacy UGM, Indonesia). The selected protein targets are RBD-S (PDB ID:6LXT), PD-ACE2 (PDB ID: 6VW1), and SARS-CoV-2 protease (PDB ID:6LU7). The affinities of bonds formed is represented as a docking score. The results show that hesperidin, one of the compounds in Citrus sp., has the lowest docking score for all three protein receptors representing the highest affinity to bind the receptors. Moreover, all of the citrus flavonoids possess good affinity to the respected receptors as well as curcumin, brazilin, and galangin, indicating that those compounds perform inhibitory potential for the viral infection and replication. In general, the results of this study indicate that Citrus sp. exhibit the best potential as an inhibitor to the development of the SARS-CoV-2, followed by galangal, sappan wood, and Curcuma sp. that can be consumed in daily life as prophylaxis of COVID-19.
Content may be subject to copyright.
Page 1 of 8
Revealing the Potency of Citrus and Galangal Constituents
to Halt SARS-CoV-2 Infection
Rohmad Yudi Utomo1,2, Muthi’ Ikawati1,3, Edy Meiyanto1,3,*
1Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada (UGM),
Sekip Utara, Yogyakarta 55281, Indonesia
2Medicinal Chemistry Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy,
UGM, Sekip Utara, Yogyakarta 55281, Indonesia
3Macromolecular Engineering Laboratory, Department of Pharmaceutical Chemistry, Faculty of
Pharmacy UGM, Sekip Utara, Yogyakarta 55281, Indonesia
*Corresponding author: edy_meiyanto@ugm.ac.id
ORCID:
Edy Meiyanto: 0000-0002-0886-6322
Rohmad Yudi Utomo: 0000-0003-4803-9417
Muthi’ Ikawati: 0000-0002-5968-0130
Abstract
COVID-19 pandemic is a serious problem in the world today. The SARS-CoV-2 virus that causes
COVID-19 has important proteins used for its infection and development, namely the protease and
spike glycoprotein. The RBD (Receptor Binding Domain) of spike glycoprotein (RBD-S) can bind to the
ACE2 (Angiotensin Converting Enzyme-2) receptor at the protease domain (PD) (PD-ACE2) of the host
cell, thereby leading to a viral infection. This study aims to reveal the potential of compounds contained
in Curcuma sp., Citrus sp., Alpinia galanga, and Caesalpinia sappan as anti SARS-CoV-2 through its
binding to 3 protein receptors. The study was conducted by molecular docking using the MOE 2010
program (licensed from Faculty of Pharmacy UGM, Indonesia). The selected protein targets are RBD-
S (PDB ID:6LXT), PD-ACE2 (PDB ID: 6VW1), and SARS-CoV-2 protease (PDB ID:6LU7). The affinities
of bonds formed is represented as a docking score. The results show that hesperidin, one of the
compounds in Citrus sp., has the lowest docking score for all three protein receptors representing the
highest affinity to bind the receptors. Moreover, all of the citrus flavonoids possess good affinity to the
respected receptors as well as curcumin, brazilin, and galangin, indicating that those compounds
perform inhibitory potential for the viral infection and replication. In general, the results of this study
indicate that Citrus sp. exhibit the best potential as an inhibitor to the development of the SARS-CoV-
2, followed by galangal, sappan wood, and Curcuma sp. that can be consumed in daily life as
prophylaxis of COVID-19.
Keywords: SARS-CoV-2; Citrus sp., Galangal, Curcuma sp., Sappan wood
Introduction
The new emerging coronavirus, SARS-CoV-2, is becoming outbreaks in entire the world, spreading
progressively across the continent of Asia, Europe, Middle East, Africa, and America covering more
than 100 countries (as reported in WHO website www.who.int; accessed on March 10, 2010; Roser &
Ritchie, 2020). The endemic of this virus invites the challenge rapidly to find the drug in concordance
with the finding of molecular characteristic of the virus. Along with the effort of the respected
researchers, we put the credit to some researchers who find the structure characteristic of spike
glycoprotein that plays an important role of the virus infection (Chan et al., 2020; Chen & Du, 2020;
Wrapp et al., 2020). This glycoprotein of SARS-CoV-2 exhibits little changes in the primary structure
compared to the beta coronavirus, SARS-CoV, due to the mutation, providing a suitable target
candidate of the new drugs (Lu et al., 2020; Xia et al., 2020).
Spike glycoprotein of SARS-CoV-2 contains Receptor Binding Domain (RBD) that recognize the target
receptor leading to the splicing of the trimeric spike protein into s1 and s2 that facilitate membrane
fusion and virus infection occurs through endocytosis (Yan et al., 2020). The receptor angiotensin-
converting enzyme 2 (ACE2) is a preferable receptor for SARS-CoV-2 spike glycoprotein than that of
spike glycoprotein of SARS-CoV due to the changes of some amino acid residues at the aa359-541,
making it more suitable to bind the receptor at the “up” position (Peng et al., 2020; Wan et al., 2020;
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 12 March 2020 doi:10.20944/preprints202003.0214.v1
© 2020 by the author(s). Distributed under a Creative Commons CC BY license.
Page 2 of 8
Wrapp et al., 2020). Therefore, the RBD of spike glycoprotein is a preferable candidate for drug target
to inhibit the initiation process of virus infection. Noted that there are many compounds have been
treated to RBD spike glycoprotein (Li & De Clercq, 2020) or under molecular docking modelling as
screening for drug candidates. However, the result showed a limited candidate to be the prospected
drugs due to the side effect threat (Smith & Smith, 2020; Wang, 2020; Senathilake et al., 2020).
Despite the spike glycoprotein, ACE2 is the other suitable candidate for drug target to prevent virus
infection. The drug candidates may target on the spike binding site that already elucidated and
simulated to bind with RBD-spike glycoprotein (Xu et al., 2020a; Yan et el., 2020). The ACE2 ligand
binding side is recognized as protease domain (PD) that playing role in the cleavage of the trimeric
structure of spike glycoprotein as the important step in virus infection (Xu et al., 2020b; Zhang et al.,
2020; Yan et al., 2020). Therefore, the inhibitory effect of some compounds to this receptor suggest to
give protection of the virus recognition.
Protease inhibitors is also suggested to be the good drug candidate to halt the virus life cycle (Qamar
et al., 2020; Haider et al., 2020). Beta coronavirus utilizes protease to cleave the structural protein
needed during viral formation in the host cells. The protease inhibitors have been developed to stop the
spreading of viruses that cause diseases such as HIV-AIDS, MERS, and SARS (Zumla et al., 2020).
Many proven drugs have been also screened with the promising result to overcome SARS-CoV-2 as
drug repurposing, such as lopinavir (HIV-AIDS drug) that is continuing in clinical study (Harrison, 2020;
Wang, 2020; Senathilake et al., 2020). Recently, the study on finding the best protease inhibitor for
SARS-CoV-2 treatment is getting more extensive by in silico model using the crystal structure of
protease domain-inhibitor complex (Chang et al., 2020; Zhavoronkov et al., 2020). This in silico
approach is still challenging in order to find more precise candidates effectively with minimal adverse
effect.
Exploring new medicines for emerging and rapidly spreading diseases such as SARS-CoV-2 could be
carried out through drug repurposing strategy to bypass the pre-clinical steps that usually require
laborious works and resources. In addition, we also need to consider developing agents which in the
future could be more easily utilized by the people. For this purpose, exploration of natural resources
that are often used by the people is the best choice. Here, we propose some common compounds from
natural products that already known to be consumed in daily life as spices or fruits. Namely
curcuminoids, the major compounds of Curcuma sp., some methoxy flavonoids, the main compounds
of Citrus sp., phenolic compounds from Caesalpinia sappan (sappan wood), and phenylpropanoid
compounds from Alpinia galanga (galangal) to be docked against 3 target proteins, RBD-S, PD-ACE2,
and SARS-CoV-2 protease. Hopefully, this result can be used as reference in developing new drug
candidates and virus prevention in daily consumption without any side effect.
Methods
Molecular docking study was chosen to be the tools for screening the binding affinity of several natural
products on SARS-CoV-2 marker protein, RBD-S, PD-ACE2, and SARS-cov-2 protease. All
computational simulation was conducted on Windows 10 Operating System, Intel Core i5-7th Gen as a
processor with 4 GB of RAM. Molecular docking study including docking simulation, RMSD calculation,
and visualization of binding interaction was performed using MOE 2010 (Licensed from Faculty of
Pharmacy UGM). The model of RBD-S used reported crystal structure with PDB ID 6VSB due to the
information of. prefusion spike glycoprotein structure containing single receptor-binding domain. The
PDB ID 6VW1 was used as the model of PD-ACE2 in complex with RBD of SARS-CoV-2. For the
crystal structure of SARS-CoV-2 protease, PDB ID 6LU7 was used which informed the structure of
protease domain in complex with protease inhibitor. The default settings were used as long as no further
explanation. The chemical structure of all chemical compounds were obtained from drawn in Chemdraw
software then subjected to conformational search and energy minimization in MOE. The docking
simulation setting used London dG and Triangle matcher as score function and placement setting
method. Forcefield method was used to refine the docking results from 30 retain setting. Results of the
molecular docking described the affinity represented by docking score and binding interaction of each
compound on the protein target.
Results and Discussion
Among the herbal medicine that commonly used in relieving diseases we choose 4 species as the
source for active constituents to be examined as its potential as anti SARS-CoV-2, namely Curcuma
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 12 March 2020 doi:10.20944/preprints202003.0214.v1
Page 3 of 8
sp., Citrus sp., Caesalpinia sappan, and Alpinia galanga. We used several representative compounds
of each plant which are known to have pharmacological benefits (Figure 1). These plants are also
believed to contribute for health and immune system among Asian people in relation to those of the
active constituents (Meiyanto & Larasati, 2019).
Figure 1. Chemical compounds used for the molecular docking screening. Current drug for SARS-CoV-2 therapy
(A). Natural compound contained in Alpinia galanga (B). Natural compound contained in Curcuma
sp.(C). Natural compound contained in Citrus sp. (D). Natural compound contained in Caesalpinia
sappan (E). ACA: Aceto Cavicol Acetate; DMC: Desmethylcurcumin; BDMC: Bisdesmethylcurcumin
We used molecular docking with 3 target receptors; SARS-CoV-2 protease (PDB:6LU7), Spike
glycoprotein-RBD (PDB:6LXT), and PD-ACE2 (PDB:6VW1); that are believed to contribute in virus
infection in comparation with the respected known ligand or drugs as references. The result showed
that several compounds could bind finely to the target receptors at the expected sides (Figure 2.). They
gave variation of the binding energies D-G (Gibbs energy) represented by the docking scores among
those of the compounds and those of the receptors (Table 1). Interestingly, we found that citrus and
galangal compounds performed superior binding affinities to each receptor compared to those of the
compounds of Curcuma sp. and sappan wood. These higher binding affinities of those of compounds
could be represent significantly of its stronger inhibitory activities to the viral infection.
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 12 March 2020 doi:10.20944/preprints202003.0214.v1
Page 4 of 8
Figure 2. Binding interaction profile of hesperidin compared to lopinavir, nafamostat, and RBD of SARS-CoV-2 on
protease domain of SARS-CoV-2 (A), Spike glycoprotein (B), and RBD-ACE2 complex (C).
Among the citrus flavonoids, hesperidin exhibited lowest energy binding with docking score of -13.51, -
9.61, and -9.50 to the respected receptor of SARS-CoV-2 protease (6LU7), Spike glycoprotein-RBD
(6LXT), and PD-ACE2 (6VW1) (Table 1). The docking score of hesperidin to SARS-CoV-2 protease
showed less than lopinavir, the repurposing drug that being conducted in clinical trial for COVID-19.
This finding suggest that hesperidin performs better interaction to the SARS-CoV-2 protease compared
to lopinavir. Besides, hesperidin also showed better interaction to Spike-RBD compared to nafamostat,
a reference compound for RBD-S binding, bringing us to consider whether hesperidin could be the new
challenge for COVID-19 targeted on triple essential receptors to abrogate virus infection and replication.
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 12 March 2020 doi:10.20944/preprints202003.0214.v1
Page 5 of 8
Table 1. Docking score of natural compounds towards several potential binding domain of SARS-CoV-2
Plant source
Ligand
Energy Gibbs (kcal/mol)
Protease Domain
(6LU7)
Spike Glycoprotein
(6LXT)
RBD-ACE2
(6VW1)
-
Lopinavir
-11.62
-
-
-
Nafamostat
-
-7.17
-
Curcuma sp.
Curcumin
-11.82
-8.39
-9.04
DMC
-11.21
-6.41
-8.04
BDMC
-11.51
-8.64
-7.48
Citrus sp.
Tangeretin
-10.55
-8.18
-6.51
Hesperetin
-12.36
-9.08
-6.71
Hesperidin
-13.51
-9.61
-9.50
Nobiletin
-10.38
-7.76
-7.88
Naringenin
-12.44
-7.40
-7.69
Caesalpinia
sappan
Brazilein
-10.52
-7.56
-7.43
Brazilin
-12.36
-7.50
-7.49
Alpinia galanga
Galangin
-12.96
-7.89
-7.60
ACA
-9.94
-6.05
-6.16
Our molecular modelling also demonstrated that brazilin, a compound found in sappan wood, and
galangin, a phenylprophane from galangal, bind to the three receptors with lower energy compared to
the respected reference compounds. These finding indicated that both compounds possess better
binding interaction and may inhibit the initial virus infection to the host cell. Moreover, we also noted
that curcumin performed better interaction to the receptors. Noted that the docking scores of all the
interaction models are still lower than that of hesperidin did, it still could be considered to have
comparable effect of those interaction models. We may include those of compounds as candidates for
further development as anti COVID-19.
All these data represent the potential inhibitory effect of Citrus sp., Curcuma sp., C. sappan, and A.
galanga on SARS-CoV-2 infection and development that may be addressed for treatment and
prevention of COVID-19. Based on the docking scores of the constituents, Citrus sp. showed the best
potency, followed by A. galanga, sappan wood, and Curcuma sp. Noted for Curcuma sp. and sappan
wood which are the main ingredients of most Indonesian traditional medicine jamu formulas, it is
commonly believed to contribute in maintaining health condition due to its antioxidant activities of their
constituents, such as curcumin in curcuma rhizome and brazilin in sappan wood (Meiyanto & Larasati,
2019). People usually consume these herbs in various drinking herbal formulas. This finding supports
the use of those medicinal plants for preventive or prophylaxis treatment against beta corona virus
infection, including SARS-CoV-2. The same antiviral potency also performed by galangal which mainly
contain galangin. Galangal has been used as spices for several food and exhibit pharmacological
benefit as anti-ageing (Ahlina et al., 2020). This finding gives us to the additional benefit of this herb for
antiviral.
Citrus sp. could be addressed as the best herb to be promoted to combat beta coronavirus, included
SARS-CoV-2, in the forms of therapeutical or prophylaxis agents. Despite hesperidin, Citrus sp.
contains several methoxy flavonoids, such as hesperetin, tangeretin, naringenin, and nobiletin which
perform low binding energy (comparable with the reference ligands, lopinavir and nafamostat) to the
three essential receptors. These low binding energies allowing those compounds to interact tightly to
the target proteins. These interactions will contribute to the inhibitory effect against virus infection and
replication. Those methoxy flavonoids exist in the whole fruit and more abundant in the peel in most of
Citrus sp. types (Nogata et al., 2006) allowing us to easily access to the sources of compounds. In
addition, those main compounds of Citrus sp. exhibit antiviral activities on several types of viruses with
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 12 March 2020 doi:10.20944/preprints202003.0214.v1
Page 6 of 8
several mechanisms (Table 2). These findings seem to be in line with and support for the findings of its
mechanism of action as an antiviral. Since, citrus fruit is a nontoxic material, it could be prepared as a
food or mixed with other herbal medicines as “jamu”. Taken together, Citrus sp. and galangal can be
used as agents to overcome the impact of the coronavirus in a form that is easily consumed so that
people can do it without special assistance.
Table 2. Antiviral activity of citrus flavonoid and other natural flavonoids
Compound
Virus
Reference
Citrus flavonoid
Hesperidin
Influenza A virus (IAV)
Dong et al.,
2014
Glucosyl
hesperidin
IAV
Saha et al.,
2009
Hesperetin
Severe acute respiratory
syndrome-coronavirus-2
(SARS-CoV-2)
Chen & Du,
2020
SARS-CoV
Lin et al., 2005
Naringenin
Dengue virus (DENV)
serotypes 1-4
Frabasile et al.,
2017
Hepatitis C virus (HCV
Rev. in Salehi
et al., 2019
Nobiletin
Hepatitis B virus (HBV)
Hu et al., 2020
Chikungunya virus (CHIKV)
Lin et al., 2017
Tangeretin
Human respiratory syncytial
virus (RSV)
Xu et al., 2015
Vesicular stomatitis virus
(VSV)
Arenavirus Lassa virus
(LASV)
Tang et al.,
2018
Other natural occurring compounds
Baicalin
SARS-CoV-2
Chen & Du,
2020
Scutellarin
SARS-CoV-2
Chen & Du,
2020
Glycyrrhizin
SARS-CoV-2
Chen & Du,
2020
Herbacetin
SARS-CoV
Jo et al., 2020
Rhoifolin
SARS-CoV
Jo et al., 2020
Pectolinarin
SARS-CoV
Jo et al., 2020
Galangin
Herpes simplex virus type 1
(HSV-1)
Mayer et al.,
1997
Coxsackie B virus type 1
(Cox B1)
Acknowledgement
This work is to support the application of those plants as nutraceuticals product under program of
Research Grant for Higher Education Applied Research [“Penelitian Terapan Unggulan Perguruan
Tinggi”] 2020 from The Ministry of Research and Technology, Indonesia awarded to EM.
References
Ahlina, F.N., Nugraheni, N., Salsabila, I.A., Haryanti, S., Da’i, M., Meiyanto, E. (2020). Revealing the
reversal effect of galangal (Alpinia galanga L.) extract against oxidative stress in metastatic
breast cancer cells and normal fibroblast cells intended as a co-chemotherapeutic and anti-
ageing agent. Asian Pacific Journal of Cancer Prevention, 21(1): 107-117. DOI:
10.31557/APJCP.2020.21.1.107
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 12 March 2020 doi:10.20944/preprints202003.0214.v1
Page 7 of 8
Chan, J.F., Kok, K., Zhu, Z., Chu, H., To, K.K., Yuan, S., Yuen, K. (2020). Genomic characterization of
the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia
after visiting Wuhan. Emerging Microbes & Infections, 9(1): 221-236. DOI:
10.1080/22221751.2020.1719902
Chang, Y., Tung, Y., Lee, K., Chen, T., Hsiao, Y., Chang, H., Hsieh, T., Su, C., Wang, S., Yu, J., Shih,
S., Lin, Yu-Hsiang, Lin, Yin-Hung, Tu, Y.E, Tung, C., Chen, C. (2020). Potential therapeutic
agents for COVID-19 based on the analysis of protease and RNA polymerase docking.
Preprints. DOI: 10.20944/preprints202002.0242.v1
Chen, H. & Du, Q. (2020). Potential natural compounds for preventing 2019-nCoV infection. Preprints,
2020: 202001.0358.v1.
Dong, W., Wei, X., Zhang, F., Hao, J., Huang, J., Zhang, C., Liang, W. (2014). A dual character of
flavonoids in influenza A virus replication and spread through modulating cell-autonomous
immunity by MAPK signaling pathways. Scientific Reports, 4: 7237. DOI: 10.1038/srep07237
Frabasile, S., Koishi, A.C., Kuczera, D., Sliveira, G.F., Verri Jr., W.A., dos Santos, C.N.D., Bordignon,
J. (2017). The citrus flavanone naringenin impairs dengue virus replication in human cells.
Scientific Reports, 7: 41864. DOI: 10.1038/srep41864
Haider, Z., Subhani, M.M., Farooq, M.A., Ishaq, M., Khalid, M., Khan, R.S.A., Niazi, A.K. (2020). In
silico discovery of novel inhibitors against main protease (Mpro0 of SARS-CoV-2 using
pharmaciphore and molecular docking based virtual screening from ZINC database. Preprints.
DOI: 10.20944/preprints202002.0431.v1
Harrison, C. (2020). Coronavirus puts drug repurposing on the fast track. Nature Biotechnology. DOI:
10.1038/d41587-020-00003-1
Hu, Z., Hu, J., Ren, F., Xu, H., Tan, M., Wang, Q, Ren, J. (2020). Nobiletin, a novel inhibitor, inhibits
HBsAg production and hepatitis B virus replication. Biochemical and Biophysical Research
Communications, 523: 802-808. DOI: 10.1016/j.bbrc.2019.12.099
Jo, S., Kim, S., Hhin, D.H., Kim, M. (2020). Inhibition of SARS-CoV 3CL protease by flavonoids. Journal
of Enzyme Inhibition and Medicinal Chemistry, 35(1): 145-151. DOI:
10.1080/14756366.2019.1690480
Li, G. & De Clercq, E. (2020). Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nature
Reviews Drug Discovery, 19: 149-150. DOI: 10.1038/d41573-020-00016-0
Lin, C., Tsai, F., Tsai, C., Lai, C., Wan, L., Ho, T., Hsieh, C., Chao, P.L. (2005). Anti-SARS coronavirus
3C-like protease effects of Isaris indigotica root and plant-derived phenolic compounds.
Antiviral Research, 68: 36-42. DOI: 10.1016/j.antiviral.2005.07.002
Lin, S., Chen, M., Li, S., Lin, C., Wang, T.W. (2017). Antiviral activity of nobiletin against chikungunya
virus in vitro. Antiviral Therapy, 22: 689-697. DOI: 0.3851/IMP3167
Meiyanto, E. & Larasati, Y. (2019). The chemopreventive activity of Indonesia medicinal plants targeting
on hallmarks of cancer. Advanced Pharmaceutical Bulletin, 9(2): 219-230. DOI:
10.15171/apb.2019.025
Meyer, J.J.M., Afoloyan, A.J., Taylor, M.B., Erasmus, D. (1997). Antiviral activity of galangin isolated
from the aerial parts of Helichrysum aureonitens. Journal of Ethnopharmacology, 56: 165-169.
Nogata, Y., Sakamoto, K., Shiratsuchi, H., Ishii, T., Yano, M., Ohta, H. (2006). Flavonoid composition
of fruit tissues of citrus species. Bioscience Biotechnology & Biochemistry, 70(1): 178-192. DOI:
10.1271/bbb.70.178
Peng C., Zhu, Z., Shi, Y., Wang, X., Mu, K., Yang, Y., Zhang, X., Xu, Z., Zhu, W. (2020). Exploring the
binding mechanism and accessible angle of SARS-CoV-2 spike and ACE2 by molecular
dynamics simulation and free energy calculation, ChemRxiv. DOI:
10.26434/chemrxiv.11877492.v1
Qamar, M.T., Alqahtani, S.M., Alamri, M.A., Chen, L. (2020). Structural basis of SARS-CoV-2 3CLpro
and anti-COVID-19 drug discovery from medicinal plants. Preprints. DOI:
10.20944/preprints202002.0193.v1
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 12 March 2020 doi:10.20944/preprints202003.0214.v1
Page 8 of 8
Roser, M. & Ritchie, H. (2020). Coronavirus Disease (COVID-19). Published online at
OurWorldInData.org. Retrieved from: 'https://ourworldindata.org/coronavirus' [Online
Resource]
Saha, R.K., Takahashi, T., Suzuki, T. (2009). Glucosyl hesperidin prevents influenza A virus replication
in vitro by inhibition of viral sialidase. Biological and Pharmaceutical Bulletin, 32(7): 1188-1192.
Salehi, B., Fokou, P.V.T., Sharifi-Rad, M., Zucca, P., Pezzani, R., Martins, N., Sharifi-Rad, J. (2019).
The therapeutic potencial of naringenin: a review of clinical trials. Pharmaceuticals, 12:11. DOI:
10.3390/ph12010011
Senathilake, K.S., Samarakoon, S.R., Tennekoon, K.H. (2020). Virtual screening of inhibitors against
spike glycoprotein of 2019 novel corona virus: a drug repurposing approach. Preprints. DOI:
10.20944/preprints202003.0042.v1
Smith, M. & Smith, J.C. (2020). Repurposing therapeutics for COVID-19: supercomputer-based docking
to the SARS-CoV-2 viral spike protein and viral spike protein-human ACE2 interface.
ChemRxiv. DOI: 10.26434/chemrxiv.11871402.v3
Tang, K., He, S., Zhang, X., Guo, J., Chen, Q., Yang, F., Banadyga, L., Zhu, W., Qiu, X., Guo, Y. (2018).
Tangeretin, an extract from Citrus peels, blocks cellular entry of arenaviruses that cause viral
hemorrhagic fever, Antiviral Research, 160: 87-93. DOI: 10.1016/j.antiviral.2018.10.011
Wan, Y., Shang, J., Graham, R., Baric, R.S., Li, F. (2020). Receptor recognition by novel coronavirus
from Wuhan: an analysis based on decade-long structures studies of SARS. Journal of
Virology. DOI: 10.1128/JVI.00127-20
Wang, J. (2020). Fast identification of possible drug treatment of coronavirus disease-19 (COVID-19)
through computational drug repurposing study, ChemRxiv. DOI:
10.26434/chemrxiv.11875446.v1
Wrapp, D., Wang, N., Corbett, K.S., Goldsmith, J.A., Hsieh, C., Abiona, O., Graham, B.S., McLellan,
J.S. (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science.
DOI: 10.1126/science.abb2507
Xia, S., Zhu, Y., Liu, M., Lan, Q., Xu, W., Wu, Y., Ying, T., Liu, S., Shi, Z., Jiang, S., Lu, L. (2020).
Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein,
Cellular & Molecular Immunology. DOI: 10.1038/s41423-020-0374-2
Xu, H., Zhong, L., Deng, J., Peng, J., Dan, H., Zeng, X., Li, T., Chen, Q. (2020a). High expression of
ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. International Journal of Oral
Science, 12: 8. DOI: 10.1038/s41368-020-0074-x
Xu, J., Liu, Z., Tang, W., Wang, G., Chung, H.Y., Liu, Q., Zhuang, L., Li, M., Li, Y. (2015). Tangeretin
from Citrus reticulate inhibits respiratory syncytial virus replication and associated inflammation
in vivo. Journal of Agricultural and Food Chemistry, 63: 9250-9257. DOI:
10.1021/acs.jafc.5b03482
Xu, X., Chen, P., Wang, J., Feng, J., Zhou, H., Li, X., Zhong, W., Hao, P., 2020b. Evolution of the novel
coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of
human transmission. Sci. China Life Sci. 63, 457460.
Yan, R., Zhang, Y., Li, Y., Xia, L., Guo, Y., Zhou, Q. (2020). Structural basis for the recognition of the
SARS-CoV-2 by full-length human ACE2. Science. DOI: 10.1126/science.abb2762
Zhang, H., Penninger, J.M., Li, Y., Zhong, N., Slutsky, A.S. (2020). Angiotensin-converting enzyme 2
(ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target.
Intensive Care Medicine. DOI: 10.1007/s00134-020-05985-9
Zhavoronkov, A., Aladinskiy, V., Zhebrak, A., Zagribelnyy, B., Terentiev, V., Bezrukov, D.S.,
Polykovskiy, D., Shayakhmetov, R., Filimonov, A., Orekhov, P., Yan, Y., Popova, O.,
Vanhaelen, Q., Aliper, A., Ivanenkov, Y. (2020). Potential COVID-2019 3C-like protease
inhibitors designed using generative deep learning approaches. ChemRxiv. DOI:
10.26434/chemrxiv.11829102.v2
Zumla, A., Chan, J.F.W., Azhar, E.I., Hui, D.S.C., Yuen, K. (2016). Coronaviruses drug discovery and
therapeutic options. Nature Reviews Drug Discovery, 15: 327-347. DOI: 10.1038/nrd.2015.37
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 12 March 2020 doi:10.20944/preprints202003.0214.v1
... exert various pharmacological actions and are extensively utilized in the TCM system. 23 Phytochemicals of Glycyrrhiza glabra, particularly the flavonoids (Glycyrrhizin, Glabridin, Liquirtigenin) and constituents including Glycyrrhizic acid and Glycyrrhetinic acid are known to have activity against the SARS-CoV. These agents act through multiple mechanisms, which include influencing the viral attachment between the host cells and spike proteins and by hindering viral replication via effects on the nucleocapsid and functional proteins. ...
... Curcumin Curcuminoids Curcuma sp. 23 ...
... Demethoxycurcumin Curcuminoids Curcuma sp. 23 ...
Article
Full-text available
SARS-CoV-2 belongs to well-known SARS Coronaviridae family. One of the main structural proteins of SARS-CoV-2 is the spike protein that is present around the surface of a viral cell and plays an essential role in viral attachment, fusion and invasion in host cell. Once a virus invades a cell, it replicates and infects other cells. The fundamental role of spike protein in the progression of viral infection has led to an increased interest in exploring agents that target the viral spike protein for effective control of CoVID-19. The related data from published articles reviewed and numerous phytochemicals that reportedly target the spike proteins of coronaviruses by computational studies briefly discussed. These active constituents possess the potential to develop as therapeutic and antiviral agents against SARS-CoV-2.
... 66 In a molecule docking study by Utomo et al to reveal the anticoronaviral significance of citrus and galangal constituents, NAR was identified to exhibit low energy binding, with a docking score to the spike glycoprotein (PDB: 6LXT) receptor of −7.40 Kcal/mol. 68 In an another study, NAR was found to have more substantial binding affinity (-9.0 kcal/mol) to viral spike glycoprotein (PDB: 6VSB) than remdesivir. 166 In a docking study by Maurya et al, NAR exhibited significant interactions with spike glycoprotein, PDB: 6VXX (MolDock score -82.10, interactions -103.13 kcal/mol), exhibiting binding interactions with Lys304, Arg765, and Thr768. ...
... 31 NAR exhibited low energy binding with a docking score of −7.69 Kcal/mol to the PD-ACE2 (PDB: 6VW1) receptor. 68 Naringin, which is the 7-O-rutinoside of NAR, exhibits the highest binding activity to the ACE2 enzyme with an estimated docking energy of −6.85 kcal/mol, with potential binding sites at Tyr515, Glu402, Glu398, and Asn394. 179 NAR interacts with Ala348, Asp350, His378, Asp382, Tyr385, Arg393, Asn394, and His401 at the active site of ACE2 (PDB:1R42), with a generated MolDock score of -83.42 kcal/mol, and interaction energy of -102.46. ...
... 192 In another study, NAR's docking with Mpro (PDB: 6LU7) showed a binding energy of −6.8 Kcal/ mol. 31 In another report, NAR exhibited low energy binding with a docking score of −12.44 Kcal/mol to the Mpro (PDB: 6LU7) receptor. 68 A virtual docking screening study related to 49 bioactive phytochemicals from several medicinal plants used in Jamu (Indonesian traditional herbal medicine) and 3CLpro (PDB: 6LU7) showed that eleven compounds exhibited good binding affinity with 3CLpro (-7.2 to −8.5 Kcal/mol), with an energy binding of 7.7 Kcal/mol for naringenin. Naringenin interacted with three hydrogen bonds (HBs) with residues Cys145, Glu166, and Asp187, van der Waal's interaction with residues His41, Pro54, Tyr54, Leu141, Asn142, Ser144, His164, Met165, Arg188, and Gln189, unfavorable donor-donor interaction with residue Gly143, cation-π interaction with residue His163, and pi-alkyl interaction with Met49. ...
Article
Full-text available
Naringenin, widely distributed in fruits and vegetables, is endowed with antiviral and other health beneficial activities, such as immune-stimulating and anti-inflammatory actions that could play a role in contributing, to some extent, to either preventing or alleviating coronavirus infection. Several computational studies have identified naringenin as one of the prominent flavonoids that can possibly inhibit internalization of the virus, virus-host interactions that trigger the cytokine storm, and replication of the virus. This review highlights the antiviral potential of naringenin in COVID-19 associated risk factors and its predicted therapeutic targets against SARS-CoV-2 infection.
... This work described that flavonoid naringin has the highest binding affinity with spike protein compared with COVID-19 common medications. 80,81 In addition, other flavonoids such as curcumin, 82 herbacetin, quercetin, kaempferol, 83-85 luteolin 86 have been proposed as potential interactions with the above-mention receptor in similar studies. ...
Article
Full-text available
Due to the absence of successful therapy, vaccines for protection are continuously being developed. Since vaccines must be thoroughly tested, viral respiratory tract infections (VRTIs), mainly coronaviruses, have seriously affected human health worldwide in recent years. In this review, we presented the relevant data which originated from trusted publishers regarding the practical benefits of functional foods (FFs) and their dietary sources, in addition to natural plant products, in viral respiratory and COVID-19 prevention and immune-boosting activities. As a result, FFs were confirmed to be functionally active ingredients for preventing COVID-19 and VRTIs. Furthermore, the antiviral activity and immunological effects of FFs against VRTIs and COVID-19 and their potential main mechanisms of action are also being reviewed. Therefore, to prevent COVID-19 and VRTIs, it is critical to identify controlling the activities and immune-enhancing functional food constituents as early as possible. We further aimed to summarize functional food constituents as a dietary supplement that aids in immune system boosting and may effectively reduce VRTIs and COVID-19 and promote therapeutic efficacy.
... Also, hesperetin, when used with chloroquine, had shown positive antiviral activity in vitro [108]. Other citrus flavonoids in lemon and orange peel, such as nobiletin, tangeretin and naringenin, have shown good affinities for SARS-CoV 3CL pro and its receptors in molecular docking studies [105,109,110]. Naringenin was described in an earlier section as one of the compounds isolated from some West African Citrus plants and reported to have antiviral activity. ...
Article
Full-text available
Objectives The recent emergence of the COVID-19 pandemic (caused by SARS-CoV-2) and the experience of its unprecedented alarming toll on humanity have shone a fresh spotlight on the weakness of global preparedness for pandemics, significant health inequalities, and the fragility of healthcare systems in certain regions of the world. It is imperative to identify effective drug treatments for COVID-19. Therefore, the objective of this review is to present a unique and contextualised collection of antiviral natural plants or remedies from the West African sub-region as existing or potential treatments for viral infections, including COVID-19, with emphasis on their mechanisms of action. Evidence acquisition Evidence was synthesised from the literature using appropriate keywords as search terms within scientific databases such as Scopus, PubMed, Web of Science and Google Scholar. Results While some vaccines and small-molecule drugs are now available to combat COVID-19, access to these therapeutic entities in many countries is still quite limited. In addition, significant aspects of the symptomatology, pathophysiology and long-term prognosis of the infection yet remain unknown. The existing therapeutic armamentarium, therefore, requires significant expansion. There is evidence that natural products with antiviral effects have been used in successfully managing COVID-19 symptoms and could be developed as anti-COVID-19 agents which act through host- and virus-based molecular targets. Conclusion Natural products could be successfully exploited for treating viral infections/diseases, including COVID-19. Strengthening natural products research capacity in developing countries is, therefore, a key strategy for reducing health inequalities, improving global health, and enhancing preparedness for future pandemics. Graphical abstract
... Other studies have found promising evidence for the therapeutic effects of curcuminoids in degenerative and autoimmune diseases involving inflammatory processes such as multiple sclerosis [9], psoriasis [10], osteoarthritis [11], ulcerative colitis [12], diabetes and cardiovascular diseases [13], cancer [14], abnormal pulmonary inflammatory responses [15] and in modulating the immune response to counteract the SARS-CoV-2 infections [16,17]. ...
Article
Full-text available
Curcuma longa constitutes an important source of secondary metabolites that have been associated with multiple health benefits. For instance, curcumin, demethoxycurcumin and bisdemethoxycurcumin, have been found to perform important biological activities, such as anti-inflammatory, antioxidant, anticancer, antimicrobial, antihypertensive and anticoagulant. These promising results prompted this research to evaluate the polyphenols of C. longa rhizomes in Costa Rica. The present work reports a comprehensive study on the polyphenolic profile and the contents of the three main curcuminoids as well as the antioxidant activity of extracts from C. longa rhizomes (n = 12) produced in Costa Rica. Through UPLC-QTOF-ESI MS, a total of 33 polyphenols were identified, grouped in eight types of structures. In addition, our findings on the main curcuminoids using UPLC-DAD show all rhizomes complying with total curcuminoids (TC) content established by the United States Pharmacopeia (USP). At an individual level, samples NW-3 and NE-1 show the higher contents (118.7 and 125.0 mg/g dry material), representing more than twice the average values of the lowest samples. These samples also exhibit the highest Folin–Ciocalteu (FC) reducing capacity results as well as the best DPPH (IC50 15.21 and 16.07 µg extract/mL) and NO (IC50 between 52.5 and 54.3 µg extract/mL) antioxidant values. Further, Pearson correlation analysis findings indicated positive correlation (p < 0.05) between TC, CUR with FC results (r = 0.833 and r = 0.867 respectively) and negative correlation (p < 0.05) between CUR, TC and FC with DPPH results (r = −0.898, r = −0.911, and r = −0.890, respectively) and between NO results and DPPH (r = −0.805, p < 0.05). Finally, results for Principal Component Analysis (PCA) showed composition variability associated with their region of origin with products from the Northeastern (NE) region exhibiting higher average values for FC, TC and antioxidant activities. Further, PCA confirmed that two samples, namely NE-1 and NW-3, stand out by presenting the highest PC1 due to their particularly high TC, CUR and antioxidant activities. Consequently, our findings agree with previous results indicating the importance of C. longa extracts to elaborate products with potential benefits for health, while delivering extracts with higher levels of curcuminoids than previous reports and exhibiting high antioxidant activity.
... 10 Moreover, curcumin has been reported to bind to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); the virus that causes COVID-19 target receptor. 11 Curcumin could therefore be a potential treatment option for patients with COVID-19. 12 In addition, it has been reported that the combination of vitamin C, curcumin and glycyrrhizic acid, promotes the production of interferons and regulates the inflammatory response, suggesting that the combination of these compounds may be useful in modulating the immune response to counteract the SARS-CoV-2 infections. ...
... Antiviral activity of curcumin was observed against different viruses including hepatitis viruses, SARS coronavirus, influenza viruses, human immunodeficiency virus (HIV), herpes simplex virus, dengue virus and chikungunya virus [36]. Utomo et al. [37] reported that curcumin binds and inhibits the target receptors including SARS-CoV-2 protease, spike glycoprotein-RBD, and PD-ACE2, which are involved in virus infection. ...
Chapter
Full-text available
Herbs and spices are plant parts (herbs from leaves and spices from other parts) that are conventionally used in their fresh or dried state for flavouring, natural condiments, preservatives and for medicinal purposes. Worldwide, most spices are classified on the basis of taste, season of growth, economic importance, growth habit and plant part used. Black pepper, chilies, small cardamom, ginger and turmeric are some of the widely used spices while common herbs include thyme, basil and bay leaves. These herbs are basically classified according to usage, active constituents and period of life. Secondary metabolites such as Eugenol, thymol, limonene, cuminaldehyde, curcumin, piperine, quercetin, luteolin in these plant parts have been found to be responsible for anticancer, antimicrobial, antiviral, antidiabetic, antioxidant, anti-inflammatory and hypocholesterolemic effects. Their application in water fortification, milk and cheese processing, production of beauty products and pesticides among others could not be underestimated. Finally, adulteration, toxicity and allergic reactions are some of the identified limitations and challenges often encountered in the use of herbs and spices.
Article
Full-text available
The propagation of the COVID-19 pandemic in Algeria has pushed the population searching alternative therapies as preventives and treatment selections. The use of medicinal plants is a promising alternative solution to strengthen immunity and chase COVID-19. The aim of this study was to carry out an ethnobotanical survey in the Bejaia department (Algeria) to identify the plants used during the current pandemic. The study was conducted from February to May 2021. The interviews were conducted with 400 informants in order to assemble socio-demographic and floristic features of the respondents and used plants. The data analysis was performed by means of Relative Frequency of Citation (RFC), Family Importance Value (FIV), and Plant Part Value (PPV). 23 medicinal plants belonging to 12 families were adopted by the population of the Bejaia localities to prevent and treat COVID-19 infection. Aloysia citriodora Palau (RFC = 0.248), Mentha spicata L. (RFC = 0.145), Citrus limon (L.) Osbeck (RFC = 0.135), Thymus vulgaris L. (RFC = 0.118), Zingiber officinalis Roscoe (RFC = 0.09), Artemisia herba-alba Asso (RFC = 0.065), and Eucalyptus globules labill (RFC = 0.063) were the most cited species. The leaves of these plants which are used (65%) in the form of infusion (43.6%) are administered orally (95.03%) to treat and relieve certain symptoms of COVID-19. The current survey is the only one in the Bejaia department regarding the exploitation of medicinal herbs in the COVID-19 pandemic. These plants can be used as a platform to manage COVID-19.
Article
Full-text available
Purpose: The unprecedented global pandemic from Covid-19 infection has generated significant chaos to humanity in both health wise and as well as economically. Thus, there have been no specific pharmacological and antiviral therapeutic option to date available for covid-19 management. For these reasons, there have been urgent needs to discover an effective medicine for preventive, and eradication methods due to the hash nature of death toll from this novel corona virus infection. Methods: Repurposing of selection, characterization of bacteria through genomic / traditional, phytochemical and fermentation methods base anti covid-19 drugs discovery. Thus, these approaches and techniques is essential to provides a better lead or otherwise. Results: Taking a bold step of faith to approach the techniques for Covid-19 methods, the results for microbiological screening of bacterial reveals that Bacillus sp (spore former, motile, rod (+) was pin-point to have the highest colony followed by Pseudomonas sp alongside with Klebsiellas sp(Capsule formers ,motile and rod (+)) and the least were found with both shigella sp (none motile, Rod (-ve) and Staphylococcus sp (cocci (+). Phytochemical screening of different plants both in qualitative and quantitative methods using Raphanu satinus, Neem (Azadirachata indica), Bagaruwa (Acacia nilotica), Moringa (Moringa oleifera) etc., respectively contain all the natural antioxidant, bioactive compounds, vitamins as well as an appreciable amount of micronutrient/ macronutrient for combatting covid-19 pandemic. Further investigation through fermentation processes were accentuated with time differences have reveal microbial crude proteins (%), pH and dry matter values have significant changes to all the specific species. Thus, there were significant increase in proteins, pH values decrease as well as dry matter decreases in this order% Protein< pH>DM respectively. Originality: in view of this current investigation anti covid-19 leads translated through microbial screening, phytochemical as well as fermentation processes could overcome the current challenges of covid-19 pandemic therapy. Considering the immense potential of phytochemical, microbiological and fermentation processes, this article summarizes the present status of the research carried out on their anti-covid-19 activities with its limitation and futuristic direction to foster drug discovery.
Article
Full-text available
The novel coronavirus disease (COVID-19) has entered a threatening stage all over the world. Many lives have been lost, and many more are in need of treatment. The mild symptoms may include fever and dry cough, but in severe cases, it could lead to pneumonia and ultimately death in some instances. Though medical scientists all over the globe are working hard to develop a treatment for this disease, yet no definite cure has been found. To date, the treatment strategy is based on adopting strategies to break the transmission of the virus and repurposing of the old drugs to prevent the loss of life. Among the various potent candidates, flavonoids may play a protective role in these times. Studies have already proven various health-promoting properties of flavonoids in earlier viral diseases, like SARS and MERS. Since ancient times, been plants have used to treat a number of human diseases. Different phytoproducts have been previously described to inhibit the replication of numerous viruses. Despite the positive reports for plant-based medications, no successful clinical trials on phytoproducts as anti-COVID agents have been conducted to date. This review highlights the efficacy of flavonoids as a treatment strategy either alone or in combination with other drugs.
Article
Full-text available
Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious epidemic COVID-19. Here we present cryo-EM structures of full-length human ACE2, in the presence of a neutral amino acid transporter B ⁰ AT1, with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 Å, with a local resolution of 3.5 Å at the ACE2-RBD interface. The ACE2-B ⁰ AT1 complex is assembled as a dimer of heterodimers, with the Collectrin-like domain (CLD) of ACE2 mediating homo-dimerization. The RBD is recognized by the extracellular peptidase domain (PD) of ACE2 mainly through polar residues. These findings provide important insights to the molecular basis for coronavirus recognition and infection.
Preprint
Full-text available
Computer Aided Drug Design (CADD) based approach to identify the drug-like compounds-inhibiting the replication of main protease (M pro) of SARS-CoV-2. Our database search using online tool "ZINC pharmer" retrieved ~1500 compounds based on pharmacophore features. Lipinski's rule was applied to further evaluate the drug-like compounds, followed by molecular docking-based screening, and the selection of screening ligand complex with M pro based on S-score (higher than reference inhibitor) and root-mean-square deviation (RMSD) value (less than reference inhibitor) using Molecular Operating Environment (MOE) system. Resultantly, ~200 compounds were identified having strong interaction with M pro of SARS-CoV-2. After evaluating their binding energy using the MOE LigX algorithm, three compounds (ZINC20291569, ZINC90403206, ZINC95480156) were identified that showed highest binding energy with M pro of SARS-CoV-2 and strong inhibition effect than the reference inhibitor. It is suggested that these candidate "drug-like compounds" have greater potential to stop the replication of SARS-CoV-2, hence might lead to the cure of COVID-19.
Article
Full-text available
It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential route of 2019-nCov infection on the mucosa of oral cavity, bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas (TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression (FANTOM5 CAGE) dataset were collected. RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. The results demonstrated that the ACE2 expressed on the mucosa of oral cavity. Interestingly, this receptor was highly enriched in epithelial cells of tongue. Preliminarily, those findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provided a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life.
Article
Full-text available
The outbreak of a novel betacoronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure (MCM) development, we determined a 3.5 Å-resolution cryo-EM structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also show biophysical and structural evidence that the 2019-nCoV S binds ACE2 with higher affinity than SARS-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable rapid development and evaluation of MCMs to address the ongoing public health crisis.
Preprint
Full-text available
The outbreak of novel coronavirus (COVID-19) infections occurring in 2019 is in dire need of finding potential therapeutic agents. In this study, we used molecular docking strategies to repurpose HIV protease inhibitors and nucleotide analogues for COVID-19. The evaluation was made on docking scores calculated by AutoDock Vina and RosettaCommons. Preliminary results suggested that Indinavir and Remdesivir have the best docking scores and the comparison of the docking sites of these two drugs shows a near perfect dock in the overlap region of the protein pocket. However, the active sites inferred from the proteins of SARS coronavirus are not compatible with the docking site of COVID-19, which may give rise to concern in the efficacy of drugs.
Preprint
The novel Wuhan coronavirus (SARS-CoV-2) has been sequenced, and the virus shares substantial similarity with SARS-CoV. Here, using a computational model of the spike protein (S-protein) of SARS-CoV-2 interacting with the human ACE2 receptor, we make use of the world's most powerful supercomputer, SUMMIT, to enact an ensemble docking virtual high-throughput screening campaign and identify small-molecules which bind to either the isolated Viral S-protein at its host receptor region or to the S protein-human ACE2 interface. We hypothesize the identified small-molecules may be repurposed to limit viral recognition of host cells and/or disrupt host-virus interactions. A ranked list of compounds is given that can be tested experimentally.<br
Preprint
The novel coronavirus (2019-nCoV) is a human and animal pathogen recently emerged in the city of Wuhan in Hubei province of China, causing a spectrum of severe respiratory illnesses. Corona viruses makes entry in to human cells through its spike (S) protein that binds to cell surface receptors. Wide spread of 2019-nCoV has been attributed to relatively high affinity of S protein to its receptor. Although S protein is a highly importantdrug target, unavailability of a high-resolution crystal structure and solvent accessible binding surface has made it a tedious target for current rapid virtual screening. A homology model of the receptor binding domain (RBD) of 2019 -n CoV S protein that is reasonably acceptable for drug screening was prepared using a high resolution crystal structure of SARS corona virus (SARS CoV)S protein. Data obtained from RBD- receptor docking experiments and published molecular dynamics experiments were used to map a RBD-receptor interaction hotspot that can be used for designing small molecule inhibitors. The hot spot was then used for virtual screening of more than 3000 drugs approved by U.S Food and Drug Administration (FDA) and other authorities for human use. Two anthracycline class drugs (zorubicin and aclarubicin) and a food dye (E 155) were predicted to be potent inhibitors of RBD – receptor interaction. Results of present study provide evidence for the potential of these compounds asprophylactic medications or for use to reduce disease severity of COVID -19.