Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds

Abstract

Background: To prioritize the development of antiviral compounds, it is necessary to compare their relative preclinical activity and clinical efficacy. Methods: We reviewed in vitro, animal model, and clinical studies of candidate anti-coronavirus compounds and placed extracted data in an online relational database. Results: As of August 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained over 2800 cell culture, entry assay, and biochemical experiments, 259 animal model studies, and 73 clinical studies from over 400 published papers. SARS-CoV-2, SARS-CoV, and MERS-CoV account for 85% of the data. Approximately 75% of experiments involved compounds with known or likely mechanisms of action, including monoclonal antibodies and receptor binding inhibitors (21%), viral protease inhibitors (17%), miscellaneous host-acting inhibitors (10%), polymerase inhibitors (9%), interferons (7%), fusion inhibitors (5%), and host protease inhibitors (5%). Of 975 compounds with known or likely mechanism, 135 (14%) are licensed in the U.S. for other indications, 197 (20%) are licensed outside the U.S. or are in human trials, and 595 (61%) are pre-clinical investigational compounds. Conclusion: CoV-RDB facilitates comparisons between different candidate antiviral compounds, thereby helping scientists, clinical investigators, public health officials, and funding agencies prioritize the most promising compounds and repurposed drugs for further development.

Current status of therapeutic monoclonal antibodies against SARS-CoV-2

“…The spike (S) protein of SARS-CoV-2 is the primary target of neutralizing antibodies (NAbs) (Fig 1A). Therefore, NAbs against SARS-CoV-2 that have either been deployed for therapy or are in advanced stage trials, for the most part, either target the receptor-binding domain (RBD) or the N-terminal domain (NTD) of the spike glycoprotein (Fig 1A and 1B) [1,2]. The S protein exists in different conformations within the host, and their nomenclatures are based on the position of RBD protein-an "up" or "down" position (Fig 1B).…”

“…The class IV NAbs do not overlap with ACE2 binding site and bind conserved region in RBD (core I region) or RBD in "up" conformation only (core II region) (Fig 1B and 1C). A complete description of these 4 classes of RBD-dependent mAbs is shown in Fig 1C . Class IV core I region-dependent NAbs have broad neutralizing activity against SARS-CoV-2, its variants, and other related coronaviruses [1][2][3]7]. Very recently, NAbs targeting new epitopes on the S2 domain (stem helix region) of spike have also been identified that are broadly neutralizing, i.e., neutralize SARS-related and other human coronaviruses (hCoVs) [8][9][10][11].…”

“…The following COVID-19 mAbs are in clinical use: bamlanivimab (LY-CoV555) [13]; bamlanivimab (LY-CoV555) and etesevimab (LY-CoV016 or JS016) [14] from Eli Lilly; casirivimab (REGN10933) and Imdevimab (REGN10987) [15] from Regeneron; cilgavimab (COV2-2130 or AZD1061) and tixagevimab (COV2-2196 or AZD8955) [16] from AstraZeneca; monotherapy-based NAbs sotrovimab (VIR-7831) [17] from GSK and Vir Biotechnology; and regdanvimab (CT-P59) [18] from Celltrion. Another set of monotherapy and combination Nabs-based therapies are under Phase III trials: 2B04 [19] and 47D11 [20] from AbbVie; BRII-196 and BRII-198 from Brii Biosciences [2]; and TY027 from Tychan are also in Phase III trials [2]. A comprehensive list of NAbs that are currently in Phase I, II, and III trials and in clinic is summarized in Fig 2A . These therapeutic mAbs are used/administered in a range of 0.5 g to 1.2 g per dose, within 10 days of symptoms onset, as monotherapy or 2.4 g as a cocktail [21][22][23].…”

Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection

“…Clinicaltrials.gov [18] was searched on 14th December 2020 using key words COVID, SARS-CoV-2 and ivermectin to identify studies. The WHO International Clinical Trials Registry Platform (ICTRP) was accessed via the COVID-NMA Initiative's mapping tool, updated to 9th December 2020, [19] and Stamford University's Coronavirus Antiviral Research Database (CoV-RDB), updated to 15th December 2020, [20] to identify additional trials listed on other national, and international registries.…”

SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma

“…The SARS-CoV-2 receptor binding domain (RBD) is the dominant target of the neutralizing response during infection 7,[10][11][12][13] . Consequently, the overwhelming majority of monoclonal neutralizing antibodies isolated thus far from infected individuals, immunoglobulin libraries, or immunized animal models, target this region 10,11,13,14 . These antibodies can be broadly divided into four main classes 15 , of which class 1 and class 2 antibodies target site I 10 epitopes that overlap with the angiotensin converting enzyme 2 (ACE2) receptor binding site.…”