COV2-2130 for COVID-19

The novel coronavirus disease (COVID-19) continues to endanger human health, and its therapeutic drugs are under intensive research and development. Identifying the efficacy and toxicity of drugs in animal models is helpful for further screening of effective medications, which is also a prerequisite for drugs to enter clinical trials. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invades host cells mainly by the S protein on its surface. After the SARS-CoV-2 RNA genome is injected into the cells, M protein will help assemble and release new viruses. RdRp is crucial for virus replication, assembly, and release of new virus particles. This review analyzes and discusses 26 anti-SARS-CoV-2 drugs based on their mechanism of action, effectiveness and safety in different animal models. We propose five drugs to be the most promising to enter the next stage of clinical trial research, thus providing a reference for future drug development.

The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the approved and potential therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary for COVID-19.

The continuous evolution of SARS-CoV-2 necessitates broadly neutralizing antibodies for robust therapeutics. In this study, we isolated 1824 single B cells from a COVID-19 convalescent donor and obtained 91 pairs of nucleotide sequences potentially encoding VH/VL domains. From this library, we generated and evaluated a panel of 38 recombinant monoclonal antibodies. Among this panel, we identified DEV_K57 as a broadly neutralizing human IgG1 antibody targeting the SARS-CoV-2 RBD. DEV_K57 exhibited in vitro neutralization breadth against diverse variants, demonstrating subnanomolar IC50 values. This in vitro efficacy was translated in vivo. In a Syrian hamster model of SARS-CoV-2 Delta infection, DEV_K57 significantly reduced viral RNA and infectious titers in both the upper and lower respiratory tracts, conferring a favorable safety profile with minimal histopathological damage. To elucidate its mechanism, we performed comprehensive biophysical and structural analyses. Biolayer interferometry revealed a high picomolar binding affinity to the RBD Delta. Furthermore, size-exclusion chromatography coupled with small-angle X-ray scattering and computational modeling uncovered a unique, stable dimeric architecture of the DEV_K57 Fab-RBD complex in solution, with a binding interface distinct from previously characterized structures. These findings underscore the value of rapid antibody isolation for pandemic preparedness against future emerging biological threats.

Abstract The emergence of SARS-CoV-2 Omicron variants has led to viral escape from many clinically approved monoclonal antibodies (mAbs) due to rapid evolution of the receptor-binding domain (RBD). Co-circulation of SARS-CoV-2 variants with unique sets of antigenic substitutions has further complicated therapeutic mAb discovery. New approaches are needed to rapidly discover and characterize mAbs with preferred specificity and functional characteristics. Here we describe and perform epitope-focused mAb discovery using glycan-masked antigens. We isolated and expressed a panel of 303 mAbs, some of which potently neutralize divergent Omicron subvariants by targeting the class 3 antigenic site on SARS-CoV-2 RBD. Epitope mapping of these antibodies revealed a spectrum of cross-reactivity and differential recognition of the class 3 site, validating the utility of this enrichment approach for targeted mAb discovery. Together, this work rationally designs glycan-masked engineered RBDs and uses them to isolate mAbs that potently neutralize antigenically divergent SARS-CoV-2 variants.