Guangdi Li

Central South University | CSU

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic strategies that target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and/or human proteins to control viral infection, encompassing hundreds of potential drugs and thousands of patients in clinical trials. So far, a few small-mol...

Hepatitis B virus (HBV) infection and type-2 diabetes (T2DM) affect millions of individuals worldwide, whereas their interplay remains largely unclear. Here, we analyzed a large cohort of 330 HBV-infected inpatients with T2DM (so-called HBV+T2DM patients) and 330 T2DM inpatients without HBV infection (T2DM patients). Poor glycemic control was defin...

Objectives: Effectiveness of oseltamivir versus peramivir in influenza-infected children remains unclear. This study aims to evaluate their effectiveness in young children (ages 0–5 years) infected with severe influenza A virus (IAV) or influenza B virus (IBV). Methods: We analyzed a cohort of 1662 young children with either IAV (N=1095) or IBV (N=...

Therapeutic and vaccine development for human poxvirus infections (e.g., monkeypox (mpox) virus, variola virus, molluscum contagiosum virus, orf virus) has been largely deserted, especially after the eradication of smallpox by 1980. Human mpox is a self-limited disease confined to Central and West Africa for decades. However, since April 2022, mpox...

Accumulating evidence suggests that SARS-CoV-2 impairs the adaptive immune system during acute infection. Still, it remains largely unclear whether the frequency and functions of T and B cells return to normal after the recovery of COVID-19. Here, we analyzed immune repertoires and SARS-CoV-2-specific neutralization antibodies in a prospective coho...

Blood transfusion safety is an essential element of public health. Current blood screening strategies rely on targeted techniques that could miss unknown or unexpected pathogens. Recent studies have demonstrated the presence of a viral community (virobiota/virome) in the blood of healthy individuals. Here, we characterized the blood virome in patie...

Pyroptosis is a form of regulated cell death mediated by the gasdermin protein family. During virus infection, cell pyroptosis restricts viral replication. The mechanisms of the tripartite motif (TRIM) protein family and IFN-stimulated genes (ISGs) against viruses have been studied. The role of TRIMs and ISGs in pyroptosis remains unclear. In this...

Despite the active development of SARS-CoV-2 surveillance methods (e.g., Nextstrain, GISAID, Pangolin), the global emergence of various SARS-CoV-2 viral lineages that potentially cause antiviral and vaccine failure has driven the need for accurate and efficient SARS-CoV-2 genome sequence classifiers. This study presents an optimized method that acc...

Objective This study aims to reveal epidemiological features and trends of liver cancer (LC) in China. Methods We retrieved data from the Global Burden of Disease database 2019. Joinpoint regression was used to examine the temporal trend of LC. Future trends of LC were estimated using the Nordpred. Results The incidence, mortality, and disability...

Under-five years of age is a critical period for children’s growth and development. Nutritional deficiency during this period is associated with wasting, underweight and stunting. We aimed to conduct an epidemiological study using data derived from the GBD2019 to found the global distribution and changing trends of nutritional deficiencies among ch...

Objective: HIV epidemiology in South-Central China is rarely reported. This study aims to characterize epidemiological and clinical features of HIV-infected patients in Hunan Province, located in South-Central China, for better management of HIV infections. Methods: This retrospective study retrieved multi-center records of laboratory-confirmed HI...

Objectives This study aims to reveal the 30-year dynamics of HBV and HCV disease burden in China from 1990 to 2019. Methods HBV/HCV data were retrieved from the Global Burden of Disease database. Joinpoint regression was used to examine temporal trends. Age-period-cohort models were applied to evaluate effects of patient age, period, and cohort on...

Background COVID-19 patients may experience “cytokine storm” when human immune system produces excessive cytokines/chemokines. However, it remains unclear whether early responses of inflammatory cytokines would lead to high or low titers of anti-SARS-CoV-2 antibodies. Methods This retrospective study enrolled a cohort of 272 hospitalized patients...

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves T follicular helper (TFH) cell‐mediated humoral immune responses. Absent in melanoma 2 (human AIM2 and murine Aim2) is a well‐known component of the inflammasome in the innate immune system. Surprisingly, we observed that in SLE patients, upregulated levels of AIM2 exp...

Background: we demonstrated that disulfide-bond A oxidoreductase-like protein (DsbA-L) was involved in the progression of renal fibrosis. However, the precise function of DsbA-L in acute kidney injury (AKI), and the mechanisms involved, have yet to be elucidated. Methods: We illustrate the DsbA-L interacted with VDAC1 by co-IP (co-immunoprecipit...

New antiviral drugs are urgently needed. Recent outbreaks caused by viruses with great epidemiological impact such as Zika, or extraordinary virulence such as Ebola, Nipah, Lassa, Crimean-Congo haemorrhagic fever highlight the current lack of clinically proven vaccines and treatments for these potentially catastrophic agents. Antiviral Discovery fo...

New antiviral drugs are urgently needed. Recent outbreaks caused by viruses with great epidemiological impact such as Zika, or extraordinary virulence such as Ebola, Nipah, Lassa, Crimean-Congo haemorrhagic fever highlight the current lack of clinically proven vaccines and treatments for these potentially catastrophic agents. Antiviral Discovery fo...

HIV reverse transcriptase (RT) inhibitors are the important components of highly active antiretroviral therapies (HAARTs) for anti-HIV treatment and pre-exposure prophylaxis in clinical practice. Many RT inhibitors and their combination regimens have been approved in the past ten years, but a review on their drug discovery, pharmacology, and clinic...

John Charles Martin should be remembered as a visionary medicinal chemist who was involved in the coinvention, development, or management of many FDA‐approved antiviral drugs such as ganciclovir, stavudine, didanosine, cidofovir, oseltamivir, adefovir dipivoxil, tenofovir disoproxil fumarate, tenofovir alafenamide, sofosbuvir, and remdesivir.

Diabetes is a noncommunicable widespread disease that poses the risk of severe complications in patients, with certain complications being life-threatening. Hepatitis C is an infectious disease that mainly causes liver damage, which is also a profound threat to human health. Hepatitis C virus (HCV) infection has many extrahepatic manifestations, in...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic of coronavirus disease in 2019 (COVID-19). Genome surveillance is a key method to track the spread of SARS-CoV-2 variants. Genetic diversity and evolution of SARS-CoV-2 were analyzed based on 260,673 whole-genome sequences, which were sampled from 62 countries bet...

Since the 1950s, great efforts have been made to develop antiviral agents against many infectious diseases such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), human cytomegalovirus (HCMV), herpes simplex virus (HSV), and varicella-zoster virus (VZV). Among the list of nearly 106 antiviral agents approved in...

Nucleoside and nucleotide analogues are essential antivirals in the treatment of infectious diseases such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV). To celebrate the 80th birthday of Prof. Dr. Erik De Clercq on 2...

The COVID-19 pandemic causes severe morbidity and mortality. This multi-country study aimed to explore risk factors that drive mortality in COVID-19 patients who received neither dexamethasone nor remdesivir. We analyzed a cohort of 568 survivors and 507 non-survivors from China, European regions, and North America. Elderly males ≥70 years accounte...

Objectives. Asymptomatic and symptomatic patients may transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their clinical features and immune responses remain largely unclear. We aimed to characterise the clinical features and immune responses of asymptomatic and symptomatic patients infected with SARS-CoV-2. Methods. We colle...

The ability to harness innate immunity is a promising solution for improving cancer immunotherapy. Interferon (IFN) induces expression of IFN-stimulated genes (ISGs) by activating the JAK-STAT signaling pathway to promote innate immunity and inhibit malignant tumor growth, but the functions and mechanisms of most ISGs in cancer regulation are unkno...

Recent studies have reported that upregulation of disulfide-bond A oxidoreductase-like protein (DsbA-L) prevented lipid-induced renal injury in diabetic nephropathy (DN). However , the role and regulation of proximal tubular DsbA-L for renal tubulointerstitial fibrosis (TIF) remains unclear. In current study, we found that a proximal tubules-specif...

The first case of COVID-19 was detected in Brazil on 25 February 2020. We report and contextualize epidemiological, demographic and clinical findings for COVID-19 cases during the first 3 months of the epidemic. By 31 May 2020, 514,200 COVID-19 cases, including 29,314 deaths, had been reported in 75.3% (4,196 of 5,570) of municipalities across all...

On June 8, 2018, an NS3/4A protease inhibitor called danoprevir was approved in China to treat the infections of HCV genotype (GT) 1b-the most common HCV genotype worldwide. Based on phase 2 and 3 clinical trials, the 12-week regimen of ritonavir-boosted danoprevir (danoprevir/r) plus peginterferon alpha-2a and ribavirin offered 97.1% (200/206) of...

Background: SARS-CoV-2 causes high mortality risk in older patients. This study aims to characterize the clinical features of older and younger SARS-CoV-2 infected patients. Results: A total of 239 patients were divided into the younger group (<60 years; n=181) and the older group (≥60 years; n=58). In both groups, fever and cough were common sy...

Multiple myeloma (MM) is a clinically and biologically heterogenous event that accounts for approximately 10% of all hematological malignancies. Chromosome 1 open reading frame 35 (C1orf35) is a gene cloned and identified in our laboratory from a MM cell line (GenBank: AY137773), but little is known about its function. In the current study, we have...

Over the past 60 years, more than 100 antiviral drugs or their combinations have been approved for clinical use. Antiviral drugs can be classified according to their chemical nature (e.g., small-molecules, peptides, biologics) or mechanisms of drug actions against specific viral proteins (e.g., polymerase inhibitors, protease inhibitors, glycoprote...

Background As an important anti-HBV drug, pegylated interferon α (PegIFNα) offers promising clinical efficacy, but biomarkers that accurately forecast treatment responses are yet to be elucidated. Here, we evaluated whether HBV RNA could act as an early monitor of pegylated interferon responses.Methods We analyzed a phase 3, multicenter, randomized...

Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV infection (now known as COVID-19), some of which are already moving into clinical trials. Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we d...

Introduction: Chemokine receptors are important therapeutic targets for the treatment of many human diseases. This study will provide an overview of approved chemokine receptor antagonists and promising candidates in advanced clinical trials. Areas covered: We will describe clinical aspects of chemokine receptor antagonists regarding their clinical...

Purpose: Despite its enormous successes, the overall response rate of cancer immunotherapy remain suboptimal, especially in breast cancer. There is an increased interest in combining immune checkpoint inhibitor with targeted agents to enhance antitumor effect. Anti-angiogenic drugs have been shown to synergize with immune checkpoint blockades, but...

Despite the implementation of various vaccination programs, hepatitis B virus (HBV) poses a considerable health problem in Saudi Arabia. Insight on HBV evolutionary history in the region is limited. We performed a comprehensive epidemiological and phylogenetic reconstruction based on a large cohort of HBV infected patients. Three hundred and ninete...

Background Portugal has one of the most severe HIV-1 epidemics in Western Europe. Two subtypes circulate in parallel since the beginning of the epidemic. Comparing their transmission patterns and its association with transmitted drug resistance (TDR) is important to pinpoint transmission hotspots and to develop evidence-based treatment guidelines....

Introduction: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are essential components of highly active antiretroviral therapy against HIV-1 infections. Here, we provide a comprehensive overview of approved and emerging NNRTIs. Areas covered: This review covers the latest trend of NNRTIs regarding their pharmacodynamics, pharmacokinetics,...

Background Portugal has one of the most severe HIV-1 epidemic in Western Europe. Two subtypes circulate in parallel since the beginning of the epidemic. Comparing their transmission patterns and its association with transmitted drug resistance (TDR) is important to pinpoint transmission hotspots and to develop evidence-based treatment guidelines....

This study aims to examine the complex relationships among verbal ability (VA), executive function (EF), and theory of mind (ToM) in young Chinese children with cochlear implants (CCI). All participants were tested using a set of nine measures: one VA, one non-VA, three EF, and four ToM. Our study cohort comprised 82 children aged from 3.8 to 6.9 y...

miRNAs are important regulators of differentiation, development and function of brown and beige fat cells. Here we identify the role of miR-199a/214 cluster in the regulation of brown and beige adipocyte development and thermogenesis in vitro and in vivo We show that expression of the miR-199a/214 cluster is dramatically decreased during brown and...

Hepatitis C virus infection is a global health issue, and there is still no available vaccine, which makes it urgent to reveal the underlying mechanisms of HCV and host factors. Although RIG-I has been recognized as the leading cytoplasmic sensor against HCV for a long time, recent findings that MDA5 regulates the IFN response to HCV have emerged....

Human innate immunity responds to viral infection by activating the production of interferons (IFNs) and proinflammatory cytokines. The mitochondrial adaptor molecule MAVS plays a critical role in innate immune response to viral infection. In this study, we show that TRIM21 interacts with MAVS to positively regulate innate immunity. Under viral inf...

Activation of innate immunity is essential for host cells to restrict the spread of invading viruses and other pathogens. However, attenuation or termination of signaling is also necessary for preventing immune-mediated tissue damage and spontaneous autoimmunity. Here, we identify NLRX1 as a negative regulator for MAVS-mediated signaling pathway du...

One of the most exciting developments in antiviral research has been the discovery of the direct-acting antivirals (DAAs) that effectively cure chronic hepatitis C virus (HCV) infections. Based on more than 100 clinical trials and real-world studies, we provide a comprehensive overview of FDA-approved therapies and newly discovered anti-HCV agents...

Beigeing of white adipose tissue has potential anti-obesity and anti-diabetes effects, yet the underlying signaling mechanisms remain to be fully elucidated. Here we show that adipose-specific knockout of Rheb, an upstream activator of mTORC1, protects mice from high fat diet-induced obesity and insulin resistance. Rheb deficiency in adipose tissue...

The introduction of highly potent direct-acting antivirals (DAAs) has revolutionized hepatitis C virus treatment. Nevertheless, viral eradication worldwide remains a challenge also in the era of DAA treatment, because of the high associated costs, high numbers of undiagnosed patients, high re-infection rates in some risk groups and suboptimal drug...

Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucle...

Despite significant progress in hepatitis C (HCV) treatment, global viral eradication remains a challenge. An in-depth map of its genome diversity within the context of structural and immunological constraints could contribute to the design of pan-genotypic antivirals and preventive vaccines. For such analyses, extensive information is only availab...

The HIV genome encodes a small number of viral proteins (i.e., 16), invariably establishing cooperative associations among HIV proteins and between HIV and host proteins, to invade host cells and hijack their internal machineries. As a known example, the HIV envelope glycoprotein GP120 is closely associated with GP41 for viral entry. From a genome-...

Introduction: Adult T-cell leukemia (ATL) is an aggressive, chemotherapy-resistant CD4+ CD25+ leukemia caused by HTLV-1 infection, which usually develops in a minority of patients several decades after infection. Recently, CD4 T stem cell memory (Tscm) cells have been identified as the hierarchical cellular apex of ATL. IFN-αα, in combination with...

Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analy...

Importance: Human cytomegalovirus has the largest genome of all viruses that infect humans. Currently, there is a great interest in establishing associations between genetic variants and strain pathogenicity of this herpesvirus. Since the number of publicly available full-genome sequences is limited, knowledge about strain diversity is highly frag...

The HIV pandemic is characterized by extensive genetic variability, which has challenged the development of HIV drugs and vaccines. Although HIV genomes have been classified into different types, groups, subtypes and recombinants, a comprehensive study that maps HIV genome-wide diversity at the population level is still lacking to date. This study...

Background A key challenge in the field of HIV-1 protein evolution is the identification of coevolving amino acids at the molecular level. In the past decades, many sequence-based methods have been designed to detect position-specific coevolution within and between different proteins. However, an ensemble coevolution system that integrates differen...

The HIV Rev protein mediates the transport of partially and unspliced HIV mRNA from the nucleus to the cytoplasm. Rev multimerizes on a secondary stem-loop structure present in the viral intron-containing mRNA species and recruits the cellular karyopherin CRM1 to export viral mRNAs from the nucleus to the cytoplasm. Previously we have identified a...