Soremekun Opeyemi S, Omolabi Kehinde F, Adewumi Adeniyi T, Soliman Mahmoud Es
Molecular Bio-computation & Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4001, Kwa-Zulu Natal, South Africa.
Future Sci OA. 2020 Nov 9;7(1):FSO640. doi: 10.2144/fsoa-2020-0079.
As coronavirus (CoV) disease 2019-associated pneumonia spreads globally, there has been an urgent need to combat the spread and develop vaccines.
MATERIALS & METHODS: We used an integrated computational algorithm to explore the binding mechanism of TMC-310911/ritonavir (RVT) with SARS-CoV-2 and SARS-CoV main proteases.
RVT and TMC-310911 had favorable interactions with the proteases, and these high interactions are facilitated by some significant residues such as Asn133, Gly195 and Gln192. Our study further implicated two important rings in the structure of RVT as a possible chemical culprit in its therapeutic activity.
Although there are conflicting clinical results on the therapeutic potency of RVT in the treatment of coronavirus disease 2019, our findings provided molecular insight into the binding mechanism of TMC-310911 and RVT with SARS-CoV-2 and SARS-CoV main proteases.
随着2019冠状病毒病相关肺炎在全球蔓延，迫切需要抗击其传播并研发疫苗。
我们使用一种综合计算算法来探究替莫考韦（TMC-310911）/利托那韦（RVT）与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）及严重急性呼吸综合征冠状病毒（SARS-CoV）主要蛋白酶的结合机制。
RVT和TMC-310911与这些蛋白酶具有良好的相互作用，并且这些高度相互作用由一些重要残基（如天冬酰胺133、甘氨酸195和谷氨酰胺192）促成。我们的研究进一步表明，RVT结构中的两个重要环可能是其治疗活性的化学根源。
尽管关于RVT治疗2019冠状病毒病的疗效存在相互矛盾的临床结果，但我们的研究结果为TMC-310911和RVT与SARS-CoV-2及SARS-CoV主要蛋白酶的结合机制提供了分子层面的见解。
