In Silico Genome Analysis Reveals the Evolution and Potential Impact of SARS-CoV-2 Omicron Structural Changes on Host Immune Evasion and Antiviral Therapeutics.
In Silico Genome Analysis Reveals the Evolution and Potential Impact of SARS-CoV-2 Omicron Structural Changes on Host Immune Evasion and Antiviral Therapeutics.
复制标题
DOI：
10.3390/v14112461
复制
发表时间：
2022-11-06
期刊：
影响因子：
--
通讯作者：
Ramaiah A
中科院分区：
文献类型：
--
作者：
Chauhan D;Chakravarty N;Jeyachandran AV;Jayakarunakaran A;Sinha S;Mishra R;Arumugaswami V;Ramaiah A
SARS-CoV-2的新变种仍在不断发展。新的SARS-CoV-2变异的关注（VOC）B.1.1.529（Omicron）是特别危险的，因为存在许多相应的突变。在这项研究中，我们使用广泛的生物信息学方法审查了约1200万SARS-CoV-2基因组和相关元数据，以了解进化和突变变化如何影响Omicron变异特性。基于子采样全球数据的分子钟分析显示，五种VOCs的进化速率为每年29.56次替换。我们观察到广泛的突变变化的刺突结构蛋白的Omicron变体。共有20%的7230个氨基酸和结构的变化，专Omicron的刺突蛋白的受体结合域（RBD）中检测到，这表明在进化过程中施加的差异选择压力。分析关键药物靶标揭示了Delta和Omicron变体之间的突变衍生的差异结合亲和力。在批准的治疗性单克隆抗体的结合位点内检测到9个单RBD置换。T细胞表位预测揭示了三个保守的非结构蛋白中的八个免疫学上重要的功能热点。基于这些区域的通用疫苗可能会保护所有这些SARS-CoV-2变体。我们观察到刺突蛋白的关键结构变化，这降低了结合亲和力，表明这些变化可能有助于病毒逃避宿主细胞免疫。这些发现强调了对SARS-CoV-2进行持续基因组监测的必要性，以更好地了解新突变如何影响病毒传播和疾病结局。
New variants of SARS-CoV-2 continue to evolve. The novel SARS-CoV-2 variant of concern (VOC) B.1.1.529 (Omicron) was particularly menacing due to the presence of numerous consequential mutations. In this study, we reviewed about 12 million SARS-CoV-2 genomic and associated metadata using extensive bioinformatic approaches to understand how evolutionary and mutational changes affect Omicron variant properties. Subsampled global data based analysis of molecular clock in the phylogenetic tree showed 29.56 substitutions per year as the evolutionary rate of five VOCs. We observed extensive mutational changes in the spike structural protein of the Omicron variant. A total of 20% of 7230 amino acid and structural changes exclusive to Omicron’s spike protein were detected in the receptor binding domain (RBD), suggesting differential selection pressures exerted during evolution. Analyzing key drug targets revealed mutation-derived differential binding affinities between Delta and Omicron variants. Nine single-RBD substitutions were detected within the binding site of approved therapeutic monoclonal antibodies. T-cell epitope prediction revealed eight immunologically important functional hotspots in three conserved non-structural proteins. A universal vaccine based on these regions may likely protect against all these SARS-CoV-2 variants. We observed key structural changes in the spike protein, which decreased binding affinities, indicating that these changes may help the virus escape host cellular immunity. These findings emphasize the need for continuous genomic surveillance of SARS-CoV-2 to better understand how novel mutations may impact viral spread and disease outcome.
登录
查看更多内容
影响因子：
5
作者：
Mariano G;Farthing RJ;Lale-Farjat SLM;Bergeron JRC
通讯作者：
Bergeron JRC
影响因子：
12.8
作者：
Kannan SR;Spratt AN;Sharma K;Chand HS;Byrareddy SN;Singh K
通讯作者：
Singh K
影响因子：
3.5
作者：
Chakravarty N;Senthilnathan T;Paiola S;Gyani P;Castillo Cario S;Urena E;Jeysankar A;Jeysankar P;Ignatius Irudayam J;Natesan Subramanian S;Lavretsky H;Joshi S;Garcia G Jr;Ramaiah A;Arumugaswami V
通讯作者：
Arumugaswami V
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
64.8
作者：
Mlcochova P;Kemp SA;Dhar MS;Papa G;Meng B;Ferreira IATM;Datir R;Collier DA;Albecka A;Singh S;Pandey R;Brown J;Zhou J;Goonawardane N;Mishra S;Whittaker C;Mellan T;Marwal R;Datta M;Sengupta S;Ponnusamy K;Radhakrishnan VS;Abdullahi A;Charles O;Chattopadhyay P;Devi P;Caputo D;Peacock T;Wattal C;Goel N;Satwik A;Vaishya R;Agarwal M;Indian SARS-CoV-2 Genomics Consortium (INSACOG);Genotype to Phenotype Japan (G2P-Japan) Consortium;CITIID-NIHR BioResource COVID-19 Collaboration;Mavousian A;Lee JH;Bassi J;Silacci-Fegni C;Saliba C;Pinto D;Irie T;Yoshida I;Hamilton WL;Sato K;Bhatt S;Flaxman S;James LC;Corti D;Piccoli L;Barclay WS;Rakshit P;Agrawal A;Gupta RK
通讯作者：
Gupta RK