SARS-CoV-2 and its variants are crossing the immunity barrier induced through vaccination. Recent Omicron sub-variants are highly transmissible and have a low mortality rate. Despite the low severity of Omicron variants, these new variants are known to cause acute post-infectious syndromes. Nowadays, novel strategies to develop new potential inhibitors for SARS-CoV-2 and other Omicron variants have gained prominence. For viral replication and survival the main protease of SARS-CoV-2 plays a vital role. Peptide-like inhibitors that mimic the substrate peptide have already proved to be effective in inhibiting the Mpro of SARS-CoV-2 variants. Our systematic canonical amino acid point mutation analysis on the native peptide has revealed various ways to improve the native peptide of the main protease. Multi mutation analysis has led us to identify and design potent peptide-analog inhibitors that act against the Mpro of the Omicron sub-variants. Our in-depth analysis of all-atom molecular dynamics studies has paved the way to characterize the atomistic behavior of Mpro in Omicron variants. Our goal is to develop potent peptide-analogs that could be therapeutically effective against Omicron and its sub-variants.

中文翻译：

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在计算机研究中使用针对 Omicron 变体主要蛋白酶的潜在肽类似物的从头设计

SARS-CoV-2 及其变种正在跨越通过疫苗接种诱导的免疫屏障。最近的 Omicron 亚变种具有高度传染性且死亡率较低。尽管 Omicron 变异的严重程度较低，但已知这些新变异会引起急性感染后综合症。如今，开发针对 SARS-CoV-2 和其他 Omicron 变体的新潜在抑制剂的新策略已受到关注。对于病毒复制和生存，SARS-CoV-2 的主要蛋白酶起着至关重要的作用。模拟底物肽的类肽抑制剂已被证明可以有效抑制 SARS-CoV-2 变体的 Mpro。我们对天然肽进行系统的经典氨基酸点突变分析，揭示了改进主要蛋白酶的天然肽的多种方法。多突变分析使我们识别和设计了有效的肽类似物抑制剂，可对抗 Omicron 亚变体的 Mpro。我们对全原子分子动力学研究的深入分析为表征 Omicron 变体中 Mpro 的原子行为铺平了道路。我们的目标是开发有效的肽类似物，对 Omicron 及其亚变体具有治疗效果。