Computational drug discovery and repurposing for the treatment of COVID-19: A systematic review

A Revisit to the Research Updates of Drugs, Vaccines, and Bioinformatics Approaches in Combating COVID-19 Pandemic

“…The mostly studied drug targets against COVID-19 include structural proteins of SARS-CoV-2 (spike glycoprotein, envelope protein, neucleocapsid protein), non-structural proteins of SARS-CoV-2 (Mpro, papain-like protease, RNA-dependent RNA polymerase, helicase), host cell target protein, and different cytokine release from host cellular environment (angiotensin-converting enzyme 2, transmembrane serine protease 2), and these are employed to both in silico and wet lab experiment for screening out effective inhibitors (Crosby et al, 2020 ; Li H. et al, 2020 ). In the present study, it has been found that Mpro (Chandel et al, 2020 ; Elmezayen et al, 2020 ; Kumar and Singh, 2020 ; Zhang D. et al, 2020 ), spike glycoprotein (S) (Hall and Ji, 2020 ; Kadioglu et al, 2020 ; Mohamed et al, 2020 ; Shah et al, 2020 ), nucleocapsid protein (Ge et al, 2020 ; Kadioglu et al, 2020 ; Musarrat et al, 2020 ; Sarma et al, 2020 ), and RNA-dependent RNA polymerase (RdRp) (Elfiky, 2020 ; Mohamed et al, 2020 ; Reiner et al, 2020 ) are the most widely studied drug targets for in silico drug development approaches, and several drug candidates suggested from computational screening are also being investigated under clinical trials ( Table 3 ).…”

“…The review study recommended that Mpro is a widely targeted drug site for COVID-19 ( Figure 1 ), and approximately 150 drug molecules have been suggested against Mpro of SARS-CoV-2 through different in silico drug repurposing techniques ( Table 3 ). Lopinavir is the mostly suggested drug molecule for Mpro as recommended in recently published literature (Barros et al, 2020 ; Biembengut and de Arruda Campos Brasil de Souza, 2020 ; Chen Y. W. et al, 2020 ; Kumar and Singh, 2020 ; Mohamed et al, 2020 ; Mothay and Ramesh, 2020 ; Ortega et al, 2020 ; Pant et al, 2020 ; Shah et al, 2020 ). Besides, ritonavir (Barros et al, 2020 ; Chen Y. W. et al, 2020 ; Kumar and Singh, 2020 ; Mohamed et al, 2020 ; Mothay and Ramesh, 2020 ; Ortega et al, 2020 ; Pant et al, 2020 ; Shah et al, 2020 ), nelfinavir (Biembengut and de Arruda Campos Brasil de Souza, 2020 ; Chandel et al, 2020 ; Kumar and Singh, 2020 ; Mittal et al, 2020 ; Mohamed et al, 2020 ; Mothay and Ramesh, 2020 ), indinavir (Biembengut and de Arruda Campos Brasil de Souza, 2020 ; Hall and Ji, 2020 ; Mamidala et al, 2020 ; Mohamed et al, 2020 ; Shah et al, 2020 ), saquinavir (Barros et al, 2020 ; Biembengut and de Arruda Campos Brasil de Souza, 2020 ; Hall and Ji, 2020 ; Ortega et al, 2020 ; Shah et al, 2020 ), grazoprevir (Ibrahim et al, 2020 ; Kadioglu et al, 2020 ; Mohamed et al, 2020 ; Shah et al, 2020 ), darunavir (Mohamed et al, 2020 ; Ortega et al, 2020 ; Pant et al, 2020 ), HCQ (Barros et al, 2020 ; Mamidala et al, 2020 ; Srivastava et al, 2020 ), raltegravir, remdesivir, rosuvastatin, amprenavir, CQ, elbasvir, fluvastatin, oseltamivir, telaprevir, tenofovir, zanamivir, ivermectin, ledipasvir, rifabutin, teniposide, and velpatasvir have been forecasted as important drug candidates for blocking Mpro of SARS-CoV-2.…”

“…About 47 drug molecules have been claimed against spike glycoprotein. It is concluded that grazoprevir could be the most potent inhibitor of spike glycoprotein, as several studies are focusing on the efficiency of blocking spike by glycoprotein (Ibrahim et al, 2020 ; Kadioglu et al, 2020 ; Mohamed et al, 2020 ; Shah et al, 2020 ). Other therapeutics such as ivermectin (Ibrahim et al, 2020 ; Kadioglu et al, 2020 ), ledipasvir, teniposide, velpatasvir (Chen Y. W. et al, 2020 ; Kadioglu et al, 2020 ), and rifabutin (Bank et al, 2020 ; Kadioglu et al, 2020 ) also showed potential inhibitory action against the spike glycoprotein of SARS-CoV-2.…”

“…Another crucial drug target is RNA-dependent RNA polymerase (RdRp), which has also been evaluated by the machine learning computational approach to identify its potential blockers ( Figure 1 ). The study revealed that favipiravir, remdesivir, and ribavirin could potentially be more potent inhibitors for RdRp (Elfiky, 2020 ; Mohamed et al, 2020 ; Reiner et al, 2020 ). Approximately six RdRp-targeted molecules were found in FDA yellow book, and six clinical trials were found to be evaluated for the safety and efficacy of newly predicted drug molecules (Elfiky, 2020 ; Mohamed et al, 2020 ; Pandit and Latha, 2020 ).…”

“…For examples, nelfinavir showed efficacy against Mpro and nucleocapsid protein (Chandel et al, 2020 ; Mittal et al, 2020 ; Mothay and Ramesh, 2020 ; Musarrat et al, 2020 ), whereas ivermectin was found to have potential against spike protein and 2′-o-ribose-methyltransferase (Chaudhary and Mishra, 2016 ; Mothay and Ramesh, 2020 ; Sharun et al, 2020 ). Grazoprevir reportedly exhibits inhibitory action against both spike protein and Mpro (Ibrahim et al, 2020 ; Kadioglu et al, 2020 ; Mohamed et al, 2020 ; Shah et al, 2020 ), whereas rifabutin was suggested against spike protein and nucleocapsid of SARS-CoV-2 (Bank et al, 2020 ; Kadioglu et al, 2020 ). About 215 clinical trial projects are ongoing in different phases on HCQ for the treatment of COVID-19 and studies leading to mixed conclusions for those candidate drugs (Gautret et al, 2020 ; Yazdany and Kim, 2020 ).…”