Agrawal Lokesh, Poullikkas Thanasis, Eisenhower Scott, Monsanto Carlo, Bakku Ranjith Kumar, Chen Min-Hua, Kalra Rajkumar Singh
Universidad Integral del Caribe y América Latina, Kaminda Cas Grandi #79, Willemstad, Curacao.
Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
Antibodies (Basel). 2021 Jan 11;10(1):3. doi: 10.3390/antib10010003.
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus for which no known effective antiviral drugs are available. In the present study, to accelerate the discovery of potential drug candidates, bioinformatics-based in silico drug discovery approaches are utilized. We performed multiple sequence alignments of the Spike (S) protein with 75 sequences of different viruses from the Orthocoronavirinae subfamily. This provided us with insights into the evolutionarily conserved domains that can be targeted using drugs or specific antibodies. Further, we analyzed the mechanism of SARS-CoV-2 core proteins, i.e., S and RdRp (RNA-dependent RNA polymerase), to elucidate how the virus infection can utilize hemoglobin to decrease the blood oxygen level. Moreover, after a comprehensive literature survey, more than 60 antiviral drugs were chosen. The candidate drugs were then ranked based on their potential to interact with the Spike and RdRp proteins of SARS-CoV-2. The present multidimensional study further advances our understanding of the novel viral molecular targets and potential of computational approaches for therapeutic assessments. The present study can be a steppingstone in the selection of potential drug candidates to be used either as a treatment or as a reference point when designing a new drug/antibody/inhibitory peptide/vaccine against SARS-CoV-2.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是一种新型冠状病毒，目前尚无已知的有效抗病毒药物。在本研究中，为了加速潜在候选药物的发现，采用了基于生物信息学的计算机辅助药物发现方法。我们将刺突（S）蛋白与来自正冠状病毒亚科的75种不同病毒的序列进行了多序列比对。这使我们深入了解了可以使用药物或特异性抗体靶向的进化保守结构域。此外，我们分析了SARS-CoV-2核心蛋白，即S蛋白和RNA依赖性RNA聚合酶（RdRp）的作用机制，以阐明病毒感染如何利用血红蛋白降低血氧水平。此外，在全面的文献调研之后，选择了60多种抗病毒药物。然后根据候选药物与SARS-CoV-2的刺突蛋白和RdRp蛋白相互作用的潜力对其进行排名。本多维研究进一步加深了我们对新型病毒分子靶点的理解以及计算方法在治疗评估中的潜力。本研究可为选择潜在的候选药物提供垫脚石，这些候选药物可用于治疗，或在设计针对SARS-CoV-2的新药/抗体/抑制性肽/疫苗时作为参考点。
