Abstract Recently, a pathogen has been identified as a novel coronavirus (SARS-CoV-2) and found to trigger novel pneumonia (COVID-19) in human beings and some other mammals. The uncontrolled release of cytokines is seen from the primary stages of symptoms to last acute respiratory distress syndrome (ARDS). Thus, it is necessary to find out safe and effective drugs against this deadly coronavirus as soon as possible. Here, we downloaded the three-dimensional model of NSP10/NSP16 methyltransferase (PDB-ID: 6w6l) and main protease (PDB-ID: 6lu7) of COVID-19. Using these molecular models, we performed virtual screening with our anti-viral, inti-infectious, and anti-protease compounds, which are attractive therapeutics to prevent infection of the COVID-19. We found that top screened compound binds with protein molecules with good dock score with the help of hydrophobic interactions and hydrogen bonding. We observed that protease complexed with Cyclocytidine hydrochloride (anti-viral and anti-cancer), Trifluridine (anti-viral), Adonitol, and Meropenem (anti-bacterial), and Penciclovir (anti-viral) bound with a good docking score ranging from −6.8 to −5.1 (Kcal/mol). Further, NSP10/NSP16 methyltransferase complexed with Telbivudine, Oxytetracycline dihydrate (anti-viral), Methylgallate (anti-malarial), 2-deoxyglucose and Daphnetin (anti-cancer) from the docking score of −7.0 to −5.7 (Kcal/mol). In conclusion, the selected compounds may be used as a novel therapeutic agent to combat this deadly pandemic disease, SARS-CoV-2 infection, but needs further experimental research. Highlights NSP10/NSP16 methyltransferase and main protease complex of SARS CoV-2 bind with selected drugs. NSP10/NSP16 methyltransferase and protease interacted with drugs by hydrophobic interactions. Compounds show good DG binging free energy with protein complexes. Ligands were found to follow the Lipinski rule of five.

中文翻译：

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针对 NSP10/NSP16 甲​​基转移酶和 SARS CoV-2 主要蛋白酶的抗病毒、抗蛋白酶和抗感染化合物的虚拟筛选、ADME/T 和结合自由能分析

摘要 最近，一种病原体被鉴定为一种新型冠状病毒 (SARS-CoV-2)，并发现它会引发人类和其他一些哺乳动物的新型肺炎 (COVID-19)。从症状的初级阶段到最后的急性呼吸窘迫综合征 (ARDS)，都可以看到细胞因子的不受控制的释放。因此，有必要尽快找到安全有效的药物来对抗这种致命的冠状病毒。在这里，我们下载了 COVID-19 的 NSP10/NSP16 甲​​基转移酶（PDB-ID：6w6l）和主要蛋白酶（PDB-ID：6lu7）的三维模型。使用这些分子模型，我们对我们的抗病毒、感染性和抗蛋白酶化合物进行了虚拟筛选，这些化合物是预防 COVID-19 感染的有吸引力的治疗方法。我们发现顶部筛选的化合物在疏水相互作用和氢键的帮助下与具有良好对接分数的蛋白质分子结合。我们观察到蛋白酶与盐酸环胞苷（抗病毒和抗癌）、曲氟尿苷（抗病毒）、阿东醇和美罗培南（抗细菌）和喷昔洛韦（抗病毒）结合，具有良好的对接评分，范围从-6.8 至 -5.1（千卡/摩尔）。此外，NSP10/NSP16 甲​​基转移酶与替比夫定、土霉素二水合物（抗病毒）、没食子酸甲酯（抗疟疾）、2-脱氧葡萄糖和瑞香素（抗癌）复合，对接评分为 -7.0 至 -5.7（千卡/摩尔） . 总之，选定的化合物可作为一种新型治疗剂来对抗这种致命的流行病 SARS-CoV-2 感染，但需要进一步的实验研究。重点介绍 NSP10/NSP16 甲​​基转移酶和 SARS CoV-2 的主要蛋白酶复合物与选定的药物结合。NSP10/NSP16 甲​​基转移酶和蛋白酶通过疏水相互作用与药物相互作用。化合物与蛋白质复合物显示出良好的 DG 结合自由能。发现配体遵循五的Lipinski规则。