Abstract
Coronavirus outbreak in December 2019 (COVID-19) is an emerging viral disease that poses major menace to Humans and it’s a crucial need to find the possible treatment strategies. Spike protein (S2), a envelop glycoprotein aids viral entry into the host cells that corresponds to immunogenic ACE2 receptor binding and represents a potential antiviral drug target. Several drugs such as antimalarial, antibiotic, anti-inflammatory and HIV-protease inhibitors are currently undergoing treatment as clinical studies to test the efficacy and safety of COVID-19. Some promising results have been observed with the patients and also with high mortality rate. Hence, there is a need to screen the best CoV inhibitors using insilico analysis. The Molecular methodologies applied in the present study are, Molecular docking, virtual screening, drug-like and ADMET prediction helps to target CoV inhibitors. The results were screened based on docking score, H-bonds, and amino acid interactions. The results shows HIV-protease inhibitors such as cobicistat (-8.3kcal/mol), Darunavir (-7.4kcal/mol), Lopinavir (-9.1kcal/mol) and Ritonavir (-8.0 kcal/mol), anti-inflammatory drugs such as Baricitinib (-5.8kcal/mol), Ruxolitinib (-6.5kcal/mol), Thalidomide (-6.5kcal/mol), antibiotic drugs such as Erythromycin(-9.0kcal/mol) and Spiramycin (-8.5kcal/mol) molecules have good affinity towards spike protein compared to antimalarial drugs Chloroquine (-6.2kcal/mol), Hydroxychloroquine (-5.2kcal/mol) and Artemisinin (-6.8kcal/mol) have poor affinity to spike protein. The insilico pharmacological evaluation shows that these molecules exhibit good affinity of drug-like and ADMET properties. Hence, we propose that HIVprotease, anti-inflammatory and antibiotic inhibitors are the potential lead drug molecules for spike protein and preclinical studies needed to confirm the promising therapeutic ability against COVID-19.
Keywords: Anti-inflammatory drugs; Antiviral drugs; COVID-19; Coronavirus; Homology modeling; Molecular docking.
【저자키워드】 COVID-19, coronavirus, Anti-inflammatory drugs, antiviral drugs, molecular docking, homology modeling, 【초록키워드】 Treatment, Baricitinib, coronavirus, Anti-inflammatory drugs, Chloroquine, Hydroxychloroquine, Anti-inflammatory, spike, Human, antiviral drugs, Lopinavir, Ritonavir, molecular docking, ACE2 receptor, Virtual screening, drug, docking, inhibitors, viral entry, antimalarial, Cobicistat, Spike protein, Artemisinin, thalidomide, Protein, Viral, outbreak, therapeutic, Clinical studies, CoV, ruxolitinib, Efficacy and safety, viral disease, glycoprotein, methodology, inhibitor, Antimalarial drugs, interactions, preclinical study, Amino acid, clinical study, antibiotic, Analysis, darunavir, lead, host cells, host cell, preclinical studies, antimalarial drug, Treatment strategies, Spiramycin, help, immunogenic, H-bonds, anti-inflammatory drug, docking score, high mortality rate, erythromycin, pharmacological, antiviral drug target, antibiotic drugs, ACE2 receptor binding, the patient, applied, screened, antibiotic drug, 【제목키워드】 coronavirus, Antiviral, spike glycoprotein, HIV protease inhibitor,