Abstract
Aims
In December 2019, the Coronavirus disease-2019 (COVID-19) virus has emerged in Wuhan, China. In this research, the first resolved COVID-19 crystal structure (main protease) was targeted in a virtual screening study by of FDA approved drugs dataset. In addition, a knowledge gap in relations of COVID-19 with the previously known fatal Coronaviruses (CoVs) epidemics, SARS and MERS CoVs, was covered by investigation of sequence statistics and phylogenetics.
Materials and methods
Molecular modeling, virtual screening, docking, sequence comparison statistics and phylogenetics of the COVID-19 main protease were investigated.
Key findings
COVID-19 Mpro formed a phylogenetic group with SARS CoV that was distant from MERS CoV. The identity% was 96.061 and 51.61 for COVID-19/SARS and COVID-19/MERS CoV sequence comparisons, respectively. The top 20 drugs in the virtual screening studies comprised a broad-spectrum antiviral (ribavirin), anti-hepatitis B virus (telbivudine), two vitamins (vitamin B12 and nicotinamide) and other miscellaneous systemically acting drugs. Of special interest, ribavirin had been used in treating cases of SARS CoV.
Significance
The present study provided a comprehensive targeting of the first resolved COVID+19 structure of Mpro and found a suitable save drugs for repurposing against the viral Mpro. Ribavirin, telbivudine, vitamin B12 and nicotinamide can be combined and used for COVID treatment. This initiative relocates already marketed and approved safe drugs for potential use in COVID-treatment.
【저자키워드】 Coronavirus disease 2019, Spike protein, nucleocapsid, membrane protein, Middle East respiratory syndrome Coronavirus, envelope, open reading frames, COVID-19coronavirus disease 2019, EEnvelope, NNucleocapsid, 2019-nCoV2019 New Coronavirus, 2019 New Coronavirus, MERS CoVMiddle East Respiratory Syndrome Coronavirus, ORFopen reading frames, Sspike protein, Mmembrane protein, 3CLpro3-C-like protease, 3-C-like protease, SARSSevere Acute Respiratory Syndrome CoV, Severe Acute Respiratory Syndrome CoV, 【초록키워드】 COVID-19, Treatment, Antiviral, knowledge, Epidemics, drugs, Virtual screening, drug, nicotinamide, docking, protease, MERS, virus, ribavirin, FDA approved drug, COVID, MPro, Research, phylogenetics, CoV, Vitamin, dataset, Phylogenetic, Safe, vitamin B12, SARS CoV, sequence, Comparisons, CoVs, material, Wuhan, China, addition, investigated, approved, provided, resolved, systemically, acting, Significance, 【제목키워드】 COVID-19, protease, FDA approved drug,