No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
COVID-19 therapy: from myths to reality and hopes
Abstract
The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, is unprecedented for the 21st century and has already affected countries with a total population of billions of people. The number of infected has already surpassed 30 million people and the number of deaths has exceeded 1 million. Unfor-tunately, Russia is still one of the five countries with the largest number of infected people, although mortality from COVID-19 is significantly lower than in many other countries. Since the virus and the pathogenesis caused by it have a lot of new and unexpected features, high-tech and specific anti-viral drugs and vaccines have not yet been created. The most promising targets for future drug development are enzymes necessary for the life cycle of this particular virus (such as components of the replicase complex or viral proteases). Unexpected circumstances are pushing the evaluation of a number of previously developed and existing drugs directed toward other RNA viruses, some of which have already been shown effective in clinical trials against SARS-CoV-2. There is no doubt that soon prototypes of drugs of this class with higher specificity and effective-ness will be found. Another group of potential drugs are known drugs that are directed against various aspects of the pathogenesis caused by SARS-CoV-2, in particular, cytokine storm or coagulopathy. It should be emphasized that the genome of the virus encodes about 10 additional proteins, some of which may be related to unusual aspects of pathogenesis during COVID-19. Basic research should determine which of these proteins can be targets for specific therapy. Finally, the fact that neutralizing antibodies are found in the blood plasma of many patients and can be used for the prevention and treatment of COVID-19, indicates the potential of using recombinant neutralizing antibodies as drugs, and secondly, confirms the possibility of creating effective vaccines. This mini-review discusses therapeutic approaches and the status of clinical trials using drugs that already existed before the pandemic and were originally developed against other infectious agents or for the treatment of autoimmune pathologies. These drugs are part of today's arsenal in therapeutic protocols and are used in an attempt to cope with the COVID-19 epidemic in different countries.
ResearchGate has not been able to resolve any citations for this publication.
Clinically approved PARP inhibitors (PARPi) have a mild adverse effect profile and are well tolerated as continuous daily oral therapy. We review the evidence that justifies the repurposing of PARPi to block the proliferation of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and combat the life‐threatening sequelae of coronavirus disease 2019 (COVID‐19) by several mechanisms. PARPi can effectively decrease IL‐6, IL‐1 and TNF‐α levels (key interleukins in SARS‐CoV‐2‐induced cytokine storm) and can alleviate subsequent lung fibrosis, as demonstrated in murine experiments and clinical trials. PARPi can tune macrophages towards a tolerogenic phenotype. PARPi may also counteract SARS‐CoV‐2‐induced and inflammation‐induced cell death and support cell survival. PARPi is effective in animal models of acute respiratory distress syndrome (ARDS), asthma and ventilator‐induced lung injury. PARPi may potentiate the effectiveness of tocilizumab, anakinra, sarilumab, adalimumab, canakinumab or siltuximab therapy. The evidence suggests that PARPi would benefit COVID‐19 patients and trials should be undertaken.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible of the coronavirus disease 2019 (COVID-19) pandemic. Therapeutic options including antimalarials, antivirals, antibiotics and vaccines are under study. Meanwhile the current pandemic has called attention over old therapeutic tools to treat infectious diseases. Convalescent plasma (CP) constitutes the first option in the current situation, since it has been successfully used in other coronaviruses outbreaks. Herein, we discuss the possible mechanisms of action of CP and their repercussion in COVID-19 pathogenesis, including direct neutralization of the virus, control of an overactive immune system (i.e., cytokine storm, Th1/Th17 ratio, complement activation) and immunomodulation of a hypercoagulable state. All these benefits of PC are expected to be better achieved if used in non-critically hospitalized patients, in the hope of reducing morbidity and mortality.
In late 2019, a new coronavirus emerged in Wuhan Province, China, causing lung complications similar to those produced by the SARS coronavirus in the 2002–2003 epidemic. This new disease was named COVID‐19 and the causative virus SARS‐CoV‐2. The SARS‐CoV‐2 virus enters the airway and binds, by means of the S protein on its surface to the membrane protein ACE2 in type 2 alveolar cells. The S protein‐ACE2 complex is internalized by endocytosis leading to a partial decrease or total loss of the enzymatic function ACE2 in the alveolar cells and in turn increasing the tissue concentration of pro‐inflammatory angiotensin II by decreasing its degradation and reducing the concentration of its physiological antagonist angiotensin 1–7. High levels of angiotensin II on the lung interstitium can promote apoptosis initiating an inflammatory process with release of proinflammatory cytokines, establishing a self‐powered cascade, leading eventually to ARDS. Recently, Gurwitz proposed the tentative use of agents such as losartan and telmisartan as alternative options for treating COVID‐19 patients prior to development of ARDS. In this commentary article, the authors make the case for the election of telmisartan as such alternative on the basis of its pharmacokinetic and pharmacodynamic properties and present an open‐label randomized phase II clinical trial for the evaluation of telmisartan in COVID‐19 patients (NCT04355936).
There are currently no proven or approved treatments for coronavirus disease 2019 (COVID‐19). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID‐19 are treated with these agents and more evidence accumulates, there continues to be no high‐quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto‐immune conditions, and provided a component in the original rationale for their use in patients with COVID‐19, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specifically, the impact of HCQ on cytokine production and suppression of antigen presentation may have immunologic consequences that hamper innate and adaptive antiviral immune responses for patients with COVID‐19. Similarly, the reported in vitro inhibition of viral proliferation is largely derived from the blockade of viral fusion that initiates infection rather than the direct inhibition of viral replication as seen with nucleoside/tide analogs in other viral infections. Given these facts and the growing uncertainty about these agents for the treatment of COVID‐19, it is clear that at the very least thoughtful planning and data collection from randomized clinical trials are needed to understand what if any role these agents may have in this disease. In this article, we review the datasets that support or detract from the use of these agents for the treatment of COVID‐19 and render a data informed opinion that they should only be used with caution and in the context of carefully thought out clinical trials, or on a case‐by‐case basis after rigorous consideration of the risks and benefits of this therapeutic approach.
Tang et al. recently reported that (Journal of Thrombosis and Haemostasis), in COVID‐19 infections caused by the novel coronavirus (SARS‐CoV‐2), heparin anticoagulant therapy lowers the mortality rate in patients who present with markedly elevated concentrations of D‐dimer 1). In other words, abnormal coagulation may influence the prognosis of COVID‐19. This is extremely interesting. The article did not describe to what extent heparin improves the abnormal coagulation and further studies by this group are anticipated. The authors reported in that article 1) and a previous article 2) that the abnormal coagulation seen in non‐survivors of COVID‐19 clearly differs from the abnormal coagulation typically seen in other severe infectious diseases.
The development of COVID-19 syndrome in anticoagulated patients, and especially their admission to intensive-care units with acute severe respiratory syndrome (SARS-CoV-2), expose them to specific problems related to their therapy, in addition to those associated with the acute viral infection. Patients on VKA hospitalized with SARS-CoV-2 show high instability of PT INR due to the variability of vitamin K metabolism, diet, fasting, co-medications, liver impairment, and heart failure. Patients on DOAC are exposed to under/over treatment caused by significant pharmacological interferences. In consideration of the pharmacological characteristics of oral anticoagulant drugs, the multiple pharmacological interactions due to the treatment of acute disease and the possible necessity of mechanical ventilation with hospitalization in intensive-care units, we suggest replacing oral anticoagulant therapies (VKA and DOAC) with parenteral heparin to avoid the risk of over/under treatment.
Antiviral drugs for managing infections with human coronaviruses are not yet approved, posing a serious challenge to current global efforts aimed at containing the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Remdesivir (RDV) is an investigational compound with a broad spectrum of antiviral activities against RNA viruses, including SARS-CoV and Middle East respiratory syndrome (MERS-CoV). RDV is a nucleotide analog inhibitor of RNA-dependent RNA polymerases (RdRps). Here, we co-expressed the MERS-CoV nonstructural proteins nsp5, nsp7, nsp8, and nsp12 (RdRp) in insect cells as a part a polyprotein to study the mechanism of inhibition of MERS-CoV RdRp by RDV. We initially demonstrated that nsp8 and nsp12 form an active complex. The triphosphate form of the inhibitor (RDV-TP) competes with its natural counterpart ATP. Of note, the selectivity value for RDV-TP obtained here with a steady-state approach suggests that it is more efficiently incorporated than ATP and two other nucleotide analogues. Once incorporated at position i, the inhibitor caused RNA synthesis arrest at position i+3. Hence, the likely mechanism of action is delayed RNA chain termination. The additional three nucleotides may protect the inhibitor from excision by the viral 3’–5’ exonuclease activity. Together, these results help to explain the high potency of RDV against RNA viruses in cell-based assays.
Importance
In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
Objective
To describe the epidemiological and clinical characteristics of NCIP.
Design, Setting, and Participants
Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020.
Exposures
Documented NCIP.
Main Outcomes and Measures
Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked.
Results
Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 10⁹/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0).
Conclusions and Relevance
In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
Obtaining full-length antibody heavy- and light-chain variable regions from individual B cells at scale remains a challenging problem. Here we use high-throughput single-cell B-cell receptor sequencing (scBCR-seq) to obtain accurately paired full-length variable regions in a massively parallel fashion. We sequenced more than 250,000 B cells from rat, mouse and human repertoires to characterize their lineages and expansion. In addition, we immunized rats with chicken ovalbumin and profiled antigen-reactive B cells from lymph nodes of immunized animals. The scBCR-seq data recovered 81% (n = 56/69) of B-cell lineages identified from hybridomas generated from the same set of B cells subjected to scBCR-seq. Importantly, scBCR-seq identified an additional 710 candidate lineages not recovered as hybridomas. We synthesized, expressed and tested 93 clones from the identified lineages and found that 99% (n = 92/93) of the clones were antigen-reactive. Our results establish scBCR-seq as a powerful tool for antibody discovery.
Middle East respiratory syndrome (MERS) is an emerging infectious disease associated with a relatively high mortality rate of approximately 40%. MERS is caused by MERS corona virus (MERS-CoV) infection, and no specific drugs or vaccines are currently available to prevent MERS-CoV infection. MERS-CoV is an enveloped virus and its envelope protein (S protein) mediates membrane fusion at the plasma membrane or endosomal membrane. Multiple proteolysis by host proteases, such as furin, transmembrane protease serine 2 (TMPRSS2), and cathepsins, causes the S protein to become fusion competent. TMPRSS2, which is localized to the plasma membrane, is a serine protease responsible for the proteolysis of S in the post-receptor binding stage. Here, we developed a cell-based fusion assay for S in a TMPRSS2-dpendent manner using cell lines expressing Renilla luciferase (RL)-based split reporter proteins. S was stably expressed in the effector cells, and the corresponding receptor for S, CD26, was stably co-expressed with TMPRSS2 in the target cells. Membrane fusion between these effector and target cells was quantitatively measured by determining the RL activity. The assay was optimized for a 384-well format, and nafamostat, a serine protease inhibitor, was identified as a potent inhibitor of S-mediated membrane fusion in a screening of about 1000 drugs approved for use by the US Food and Drug Administration. Nafamostat also blocked MERS-CoV infection in vitro. Our assay has the potential to facilitate the discovery of new inhibitors of membrane fusion of MERS-CoV as well as other viruses that rely on the activity of TMPRSS2.
The 5′ m7G cap is an evolutionarily conserved modification of eukaryotic mRNA. Decades of research have established that the
m7G cap serves as a unique molecular module that recruits cellular proteins and mediates cap-related biological functions
such as pre-mRNA processing, nuclear export and cap-dependent protein synthesis. Only recently has the role of the cap 2′O
methylation as an identifier of self RNA in the innate immune system against foreign RNA has become clear. The discovery of
the cytoplasmic capping machinery suggests a novel level of control network. These new findings underscore the importance
of a proper cap structure in the synthesis of functional messenger RNA. In this review, we will summarize the current knowledge
of the biological roles of mRNA caps in eukaryotic cells. We will also discuss different means that viruses and their host
cells use to cap their RNA and the application of these capping machineries to synthesize functional mRNA. Novel applications
of RNA capping enzymes in the discovery of new RNA species and sequencing the microbiome transcriptome will also be discussed.
We will end with a summary of novel findings in RNA capping and the questions these findings pose.
COVID‐19 leads to mortality of several patients and the cytokine storm is reportedly critical in the patients. In order to reduce the cytokine storm, we would like to propose the IL6 receptor antagonist therapy for the COVID‐19 patients. Two humanized monoclonal antibodies are in clinical trial following IL6R antagonist therapies namely tocilizumab and sarilumab. However, researchers and physicians should look for more IL6 receptor antagonists for the therapy of cytokine storm syndrome SARS‐CoV‐2 infected persons to enhance the therapeutic options for cytokine storm.
This article is protected by copyright. All rights reserved.
Background
Accumulating evidence proposed JAK inhibitors as therapeutic targets warranting rapid investigation.
Objective
This study evaluated the efficacy and safety of ruxolitinib, a Janus-associated kinase (JAK1/2) inhibitor, for COVID-19.
Methods
We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe COVID-19.
Results
Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus SoC treatment (22 patients) or placebo based on SoC treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in intervention group and 21 patients in control group were included in the study. Treatment with ruxolitinib plus SoC was not associated with significantly accelerated clinical improvement in severe patients with COVID-19, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed CT improvement at D14 compared with 13 (61.9%) patients from the control group (P = 0.0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at D28; no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines were significantly decreased in the ruxolitinib group in comparison to the control group.
Conclusions
Although no statistical difference was observed, ruxolitinib recipients had a numerically faster clinical improvement. Significant chest CT improvement, a faster recovery from lymphopenia and favorable side-effect profile in ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population.
This trial is registered at www.chictr.org.cn as ChiCTR-OPN-2000029580.
Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID‐19) and have a more severe clinical course once infected. Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID‐19 with higher percentages, 25%–35% or more, when patients critically ill or with concomitant cardiac disease are considered. Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by the exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID‐19. A key role may be that of the renin–angiotensin‐aldosterone system. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infects human cells binding to angiotensin‐converting‐enzyme 2 (ACE2), an enzyme responsible of the cleavage of angiotensin II into angiotensin 1–7, which has vasodilating and anti‐inflammatory effects. Virus‐mediated downregulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper‐inflammatory reaction of COVID‐19. On the other hand, ACE2 may be upregulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers. ACE2 upregulation may increase the susceptibility to COVID‐19 but may be also protective versus angiotensin II mediated vasoconstriction and inflammatory activation. Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID‐19 infection and severity. Prospective trials are needed to ascertain whether these drugs may have protective effects.
This article is protected by copyright. All rights reserved.
We read with interest the International Society on Thrombosis and Hemostasis interim guidance on recognition and management of coagulopathy in COVID‐19 (1). We applaud this group’s efforts in releasing a timely article on the pandemic impacting all regions of the globe. While we agree that this interim guidance addresses important considerations for monitoring the disease process, we believe that the proposed treatment strategy of prophylactic low molecular weight heparin (LMWH) to treat severe COVID‐19 coagulopathy is an unconvincing strategy. Patients that are critically ill with COVID‐19 have hallmark signs of disseminated intravascular coagulation (DIC)(2), and as noted in the ISTH interim guidance and our own clinical practice, thrombosis is the overwhelming phenotype with rare bleeding complications. We address this concern with the existing data on the severe hypercoagulable state of COVID‐19 victims and advocate for consideration of systemic anticoagulation with unfractionated heparin to prevent life threatening micro‐ and macrovascular thrombosis to mitigate their associated consequences, up to and including progression of respiratory and organ failure.
Major therapeutic developments have been achieved in the field of thrombotic and hemorrhagic diseases over the last decade. These include the development and validation of four direct oral anticoagulants (DOACs) indicated for numerous thrombotic disorders, both arterial and venous [1]. It also involves new haemostatic agents for hemophilia patients, in particular Factor VIII (FVIII) and Factor IX (FIX) concentrates with extended half‐life (EHL) [2;3] and a bispecific antibody mimicking the action of FVIII (Emicizumab) [4;5].
Angiotensin Receptor Blockers (ARBs) exhibit major pleiotropic protecting effects beyond their antihypertensive properties, including reduction of inflammation. ARBs directly protect the lung from the severe acute respiratory syndrome as a result of viral infections, including those from coronavirus. The protective effect of ACE2 is enhanced by ARB administration. For these reasons ARB therapy must be continued for patients affected by hypertension, diabetes and renal disease, comorbidities of the current 2019-nCoV pandemic. Controlled clinical studies should be conducted to determine whether ARBs may be included as additional therapy for 2019-nCoV patients.
An outbreak of 2019‐nCoV infection in China has spread across the world. No specific antiviral drugs have been approved for the treatment of COVID‐2019. In addition to the recommended antiviral drugs such as interferon‐ɑ, lopinavir/ritonavir, ribavirin, and chloroquine phosphate, some clinical trials focusing on virus RNA dependent RNA polymerase (RdRp) inhibitors have been registered and initiated. Favipiravir, a purine nucleic acid analog and potent RdRp inhibitor approved for use in influenza, is also considered in several clinical trials. Herein, we summarized the pharmacokinetic characteristics of favipiravir and possible drug‐drug interactions from the view of drug metabolism. We hope this will be helpful for the design of clinical trials for favipiravir in COVID‐2019, as data regarding in vitro virus inhibition and efficacy in preclinical animal studies are still not available.
The novel corona virus infection (now classified as COVID‐19), first identified in December 2019 in Wuhan, China, has contributed to significant mortality in several countries with the number of infected cases increasing exponentially worldwide.¹ The majority of the most severely ill patients initially present with single organ failure (i.e. respiratory insufficiency) but some of them progress to more systemic disease and multiple organ dysfunction. One of the most significant poor prognostic features in those patients is the development of coagulopathy.² In patients who develop sepsis from various infectious agents, development of coagulopathy is one of the key and persistent features which is associated with poor outcomes.³ In this context, the role of International Society of Thrombosis and Haemostasis (ISTH) would be crucial in guiding health care professionals how to manage the coagulopathy of COVID‐19. A simple and easily follow‐able algorithm for the management of COVID‐19 coagulopathy would currently be useful in both the well‐resourced and less‐resourced settings as a guide in managing this complication. This pragmatic statement should clearly be considered as an interim guidance since the clinical experience of managing this pandemic is increasing. The authors are certain that this statement will be modified with developing knowledge and therapeutics in managing COVID‐19. The aim of this guidance document is to provide a risk stratification at admission for a COVID‐19 patient and management of coagulopathy which may develop in some of these patients, based on easily available laboratory parameters.
The hemagglutinin (HA) and neuraminidase (NA) of influenza A viruses induce antibodies which augment the uptake of influenza A virus by antigen presenting cells via Fc receptor entry. Antibody-dependent enhancement of uptake of virus by cells was mediated by Fc receptors because F(ab')2 preparations of lgG mixed with virus did not enhance virus uptake. The enhanced infection was measured using a fluorescent focus assay and was confirmed by dot-blot hybridization analysis. A 25-fold increase in the number of cells containing influenza antigens was detected when virus was mixed with subneutralizing concentrations of immune serum to the homologous virus before adding to neuraminidase-treated cells. Infection was also augmented using reassortant viruses which shared only the HA or the NA of the virus used to induce antibodies. Specific antisera to purified HA or NA also enhanced virus uptake. These results indicate that both the HA and the NA induce antibodies that enhance uptake of virus by Fc receptor bearing cells. In addition we determined that the drift of neutralizing antigens occurred more quickly than the drift of infection-enhancing antigens during the evolution of virus strains of the H3 subtype. The increase in the number of antigen presenting cells as a result of uptake of virus complexed with cross-reactive enhancing antibodies may affect the T cell responses to influenza infection.
MERS-CoV (подрод Merbecovirus) // Вопросы вирусологии, 2020. Т. 65, № 2. С. 62-70
- Д К Львов
- С В Альховский
Львов Д.К., Альховский С.В. Истоки пандемии COVID-19: экология и генетика коронавирусов (Betacoronavirus: Coronaviridae) SARS-CoV, SARS-CoV-2 (подрод Sarbecovirus), MERS-CoV (подрод
Merbecovirus) // Вопросы вирусологии, 2020. Т. 65, № 2. С. 62-70. [Lvov D.K., Alkhovsky S.V. Source of the
COVID-19 pandemic: ecology and genetics of coronaviruses (Betacoronavirus: Coronaviridae) SARS-CoV, SARS-CoV-2 (subgenus Sarbecovirus), and MERS-CoV (subgenus Merbecovirus). Voprosy virusologii = Problems of
Virology, 2020, Vol. 65, no. 2, pp. 62-70. (In Russ.)]
Elfiky A.A. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): a molecular docking study
2020, Т. 22, № 5
12. Elfiky A.A. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA
dependent RNA polymerase (RdRp): a molecular docking study. Life Sci., 2020, Vol. 253, 117592. doi: 10.1016/j.
lfs.2020.117592.
Novel coronavirus treatment with ribavirin: groundwork for an evaluation concerning COVID-19
- P Horby
- W S Lim
- J Emberson
- M Mafham
- J Bell
- L Linsell
- N Staplin
- C Brightling
- A Ustianowski
- E Elmahi
- B Prudon
- C Green
- T Felton
- D Chadwick
- K Rege
- C Fegan
- L C Chappell
- S N Faust
- T Jaki
- K Jeffery
- A Montgomery
- K Rowan
- E Juszczak
- J K Baillie
- R Haynes
- M J Landray
- R C Group
Horby P., Lim W.S., Emberson J., Mafham M., Bell J., Linsell L., Staplin N., Brightling C., Ustianowski A.,
Elmahi E., Prudon B., Green C., Felton T., Chadwick D., Rege K., Fegan C., Chappell L.C., Faust S.N., Jaki T., Jeffery K.,
Montgomery A., Rowan K., Juszczak E., Baillie J.K., Haynes R., Landray M.J., Group R.C. Effect of Dexamethasone
in hospitalized patients with COVID-19: preliminary report. N. Engl. J. Med., 2020. doi: 10.1056/NEJMoa2021436.
18. Khalili J.S., Zhu H., Mak N.S.A., Yan Y., Zhu Y. Novel coronavirus treatment with ribavirin: groundwork for
an evaluation concerning COVID-19. J. Med. Virol., 2020, Vol. 92, no. 7, pp. 740-746.