Hypothetical targets and plausible drugs of coronavirus infection caused by SARS‐CoV‐2

Abstract

The world is confronting a dire situation due to the recent pandemic of the novel coronavirus disease (SARS‐CoV‐2) with the mortality rate passed over 470,000. Attaining efficient drugs evolve in parallel to the understanding of the SARS‐CoV‐2 pathogenesis. The current drugs in the pipeline and some plausible drugs are overviewed in this paper. Although different types of anti‐viral targets are applicable for SARS‐CoV‐2 drug screenings, the more promising targets can be considered as 3C‐like main protease (3Cl protease) and RNA polymerase. The remdesivir could be considered the closest bifunctional drug to the provisional clinical administration for SARS‐CoV‐2. The known molecular targets of the SARS‐CoV‐2 include fourteen targets, while four molecules of angiotensin‐converting enzyme 2 (ACE2), cathepsin L, 3Cl protease and RNA‐dependent RNA polymerase (RdRp) are suggested as more promising potential targets. Accordingly, dual‐acting drugs as an encouraging solution in drug discovery are suggested. Emphasizing the potential route of SARS‐CoV‐2 infection and virus entry‐related factors like integrins, cathepsin and ACE2 seems valuable. The potential molecular targets of each phase of the SARS‐CoV‐2 life cycle are discussed and highlighted in this paper. Much progress in understanding the SARS‐CoV‐2 and molecular details of its life cycle followed by the identification of new therapeutic targets are needed to lead us to an efficient approach in anti‐SARS‐CoV‐2 drug discovery.

Introduction and Characteristics of SARS-CoV-2 in North-East of Romania During the First COVID-19 Outbreak

“…The antiviral function of BST-2, in the case of SARS-CoV, occurs by stopping the egression of virions through the plasma membrane and inhibits glycosylation of BST-2 while removes its antiviral function ( Taylor et al, 2015 ). Although ORF7a was proposed as a potential candidate for antiviral drug development ( Almasi and Mohammadipanah, 2020 ), other groups have reported significant mutations in ORF7a ( Holland et al, 2020 ).…”

Analysis of genome characteristics and transmission of SARS-CoV-2 strains in North-East of Romania during the first COVID-19 outbreak

“…The antiviral function of BST-2, in the case of SARS-CoV, occurs by stopping the egression of virions through the plasma membrane and inhibits glycosylation of BST-2 while removes its antiviral function [39]. Although ORF7a was proposed as a potential candidate for antiviral drug development [40], other groups have reported significant mutations in ORF7a [41].…”

Comparative effectiveness of pharmacological interventions on mortality and the average length of hospital stay of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials

“…They act through various pathways on whole infection process. [ 12 , 14 , 26 , 27 ] Hydroxychloroquine 1- An inhibitor of ACE-II and spike protein by affecting the terminal glycosylation 2- An inhibitor of viral particles release 3- Anti-inflammatory effect Malaria [ 12 , 14 , 28 ] Anti- inflammatory Leflunomide An inhibitor of dihydroorotate dehydrogenase Rheumatoid arthritis Inflammatory responses are suppressed through acting on different inflammatory compartments and commonly are used as anti-inflammatory drugs. [ 29 ] Hydrocortisone An inhibitor of various inflammatory factors (phospholipase A2, NF-kappa B, etc.)…”