Abstract
Effective, safe, and pharmacokinetically suitable drugs are urgently needed to curb the ongoing COVID-19 pandemic. The main protease or 3C-like protease (Mpro or 3CLpro) of SARS-CoV-2 is considered an important target to formulate potent drugs corresponding to its crucial role in virus replication and maturation in addition to its relatively conserved active site. Promising baseline data on the potency and safety of drugs targeting SARS-CoV-2 Mpro are currently available. However, preclinical and clinical data on the pharmacokinetic profiles of these drugs are very limited. This review discusses the potency, safety, and pharmacokinetic profiles of potential inhibitors of SARS-CoV-2 Mpro and forward directions on the development of future studies focusing on COVID-19 therapeutics.
Highlights
Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is causing significant social, economic, and political disturbances worldwide
Several antivirals and immune modulators are being considered for clinical use (Connelly, 2020)
Determining the potency, safety, and pharmacokinetic profiles of drugs and applying it into clinical practice is the ultimate aim of drug discovery
Summary
Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is causing significant social, economic, and political disturbances worldwide. Remdesivir helps fast recovery of moderate and severely affected patients but its clinical effect on nonmechanically ventilated severely affected patients is optimal (Elsawah et al, 2020). This indicates that the treatment of COVID-19 is still medically unmet requiring further efforts. Patient management is primarily dependent on symptomatic treatment and respiratory support including intensive care in case of complicated disease (Cascella et al, 2020; Chen et al, 2020; Gattinoni et al, 2020). Fifteen drugs (chloroquine, hydroxychloroquine, lopinavir, ritonavir, nafamostat, camostat, famotidine, umifenovir, nitazoxanide, ivermectin, corticosteroids, tocilizumab, sarilumab, bevacizumab, and Potency of SARS-CoV-2 Mpro inhibitors fluvoxamine) are under clinical trial (Shaffer, 2020) for COVID19 treatment. Several antivirals (bemcentinib, chloroquine and hydroxychloroquine, lopinavir boosted with ritonavir and remdesivir) and immune modulators (anakinra and canakinumab, azithromycin, brensocatib, convalescent plasma, corticosteroids, interferon beta, ruxolitinib, mesenchymal stromal cells and sarilumab and tocilizumab) are being considered for clinical use (Connelly, 2020)
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