| Popis: |
divInfection with SARS-CoV-2 has resulted in COVID-19 pandemic and infected more than 5/divdivmillion individuals with around 0 35 million deaths worldwide till May 2020 end Several/divdivefforts are on in search of therapeutic interventions, but the preferred way is drug/divdivrepurposing due to the feasibility and urgency of the situation To select and prioritize/divdivapproved antiviral drugs and drug combinations for COVID-19, 61 antiviral drugs having/divdivproven safety profile in humans were subjected to virtual screening for binding to three/divdivselect targets namely human angiotensin-converting enzyme receptor-2 receptor-binding/divdivdomain (hACE-2) involved in virus entry, SARS-CoV-2 RNA dependent RNA polymerase/divdiv(RdRp) responsible for viral RNA replication and SARS-CoV-2 main protease (MPro) causing/divdivproteolytic processing of viral polyprotein slab Targeting multiple ‘disease pathogenesis/divdivspecific proteins’ within a close network of interaction or having dependent functionality can/divdivprovide effective intervention Ledipasvir, Daclatasvir, Elbasvir, Paritaprevir, Rilpivirine and/divdivIndinavir were identified as candidate drugs of interest for COVID-19 based on a derived/divdivcombined activity score, pharmacokinetic and pharmacodynamic parameters Ledipasvir and/divdivDaclatasvir and their approved marketed combination with Sofosbuvir emerged as leading/divdivcandidate drugs/drug combinations for SARS-CoV-2 These candidates have the potential/divdivfor the antiviral activity for SARS-CoV-2 infection better than the investigational drug/divdivRemdesivir and other antiviral drugs/drug combinations being evaluated These/divdivdrugs/combinations merit systematic fast track preclinical and clinical evaluation for COVID-/divdiv19 management The present work brings back attention to the potential usefulness of/divdivapproved antiviral drugs/drug combinations, commonly available with established safety/divdivprofile, currently not in focus for COVID-19 It provides a rationale based approach for the/divdivselection of drugs with potential antiviral activity against SARS-CoV-2 highlighting the/divdivdesired properties /div |
