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 July 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained >2,400 cell culture, entry assay and biochemical experiments, 240 animal model studies, and 56 clinical studies from >300 published papers. SARS-CoV-2, SARS-CoV, and MERS-CoV account for approximately 85% of the data. Approximately 75% of experiments involved compounds with a known or likely mechanism of action, including receptor binding inhibitors and monoclonal antibodies (20%); viral protease inhibitors (18%); polymerase inhibitors (9%); interferons (8%); fusion inhibitors (8%); host endosomal trafficking inhibitors (7%); and host protease inhibitors (5%). For 724 compounds with a known or likely mechanism, 95 (13%) are licensed in the US for other indications, 72 (10%) are licensed outside the US or are in human trials, and 557 (77%) 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.

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 – 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.…”

SARS-CoV-2 RNA-dependent RNA polymerase as a therapeutic target for COVID-19

“…References are indicated in square brackets. Additional data based on non-peer-reviewed manuscripts can be found at the Coronavirus Antiviral Research Database website [ https://covdb.stanford.edu/ [ 32 ] SARS-COV-2 Drug (alternative names) Original patent application number FDA approval In vitro activity (range IC 50 , µM) In vivo activity Number of clinical trials Non-human cells Human cells Host Lung titer Swab titer Completed Ongoing Remdesivir (GS-5734; Veklury) WO 2016161176 SARS-COV-2 0.3–27[ 33–46 ] 0.003–1.3[ 35 , 39 , 40 , 47 , 48 ] Mice [ 35 ] and rhesus macaque[ 49 ] Decreased Decreased 5 27 Molnupiravir (EIDD-2801) WO 2017156380 NA 0.3 [ 38 , 50 ] 0.02–0.09 [ 50 ] Mice [ 50 ] Decreased Decreased 1 2 Favipiravir (Avigan; Favipira; T-705) ...…”

Structural and Biochemical Rationale for Enhanced Spike Protein Fitness in Delta and Kappa SARS-CoV-2 Variants

“…The Kappa variant, despite harbouring multiple mutations in the S protein that have been demonstrated to increase viral fitness, has not significantly spread globally, with only a few travel-linked clusters reported 5, 6, 7 . The exact mutations present within the Kappa and Delta S proteins have been reported variously, suggesting a degree of variability in their classification 8, 9, 10, 11, 12 . Within the receptor-binding domain (RBD) of the S protein, both the Kappa and Delta variants share an identical substitutional mutation (L452R) with the previously emerged variants of interest B.1.427/429 (Epsilon) 1,2,4,8 .…”