Rationale Based Selection and Prioritization of Antiviral Drugs for COVID-19 Management

Infection with SARS-CoV-2 has resulted in COVID-19 pandemic and infected more than 5

million individuals with around 0.35 million deaths worldwide till May 2020 end. Several

efforts are on in search of therapeutic interventions, but the preferred way is drug

repurposing due to the feasibility and urgency of the situation. To select and prioritize

approved antiviral drugs and drug combinations for COVID-19, 61 antiviral drugs having

proven safety profile in humans were subjected to virtual screening for binding to three

select targets namely human angiotensin-converting enzyme receptor-2 receptor-binding

domain (hACE-2) involved in virus entry, SARS-CoV-2 RNA dependent RNA polymerase

(RdRp) responsible for viral RNA replication and SARS-CoV-2 main protease (MPro) causing

proteolytic processing of viral polyprotein slab. Targeting multiple ‘disease pathogenesis

specific proteins’ within a close network of interaction or having dependent functionality can

provide effective intervention. Ledipasvir, Daclatasvir, Elbasvir, Paritaprevir, Rilpivirine and

Indinavir were identified as candidate drugs of interest for COVID-19 based on a derived

combined activity score, pharmacokinetic and pharmacodynamic parameters. Ledipasvir and

Daclatasvir and their approved marketed combination with Sofosbuvir emerged as leading

candidate drugs/drug combinations for SARS-CoV-2. These candidates have the potential

for the antiviral activity for SARS-CoV-2 infection better than the investigational drug

Remdesivir and other antiviral drugs/drug combinations being evaluated. These

drugs/combinations merit systematic fast track preclinical and clinical evaluation for COVID-

19 management. The present work brings back attention to the potential usefulness of

approved antiviral drugs/drug combinations, commonly available with established safety

profile, currently not in focus for COVID-19. It provides a rationale based approach for the

selection of drugs with potential antiviral activity against SARS-CoV-2 highlighting the

desired properties.

Abstract