Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals.
Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals.
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DOI：
10.1038/s41467-022-30865-9
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发表时间：
2022-06-08
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
尽管最近使用抗病毒药物治疗丙型肝炎病毒（HCV）取得了成功，但仍然需要HCV疫苗来预防治疗患者的再感染，避免耐药菌株的出现，并为无法获得抗病毒治疗的人提供保护。广泛中和抗体（bNAb）的早期产生与HCV清除相关。几种有效的bNAb使用含有环内二硫键的不寻常的重链互补决定区3（HCDR 3）结合保守的HCV糖蛋白E2表位。另外的结构同源bNAb的分离将有助于识别此类bNAb的关键决定簇并指导合理的疫苗设计。在这里，我们报告的识别新的抗体含有HCDR3二硫键基序使用计算筛选与Rosetta软件。使用新发现的和已知的这个抗体家族的成员，我们审查所需的HCDR3的氨基酸组成，并提出决定因素的弯曲与直HCDR3环构象中观察到的这些抗体。确定丙型肝炎病毒（HCV）广泛中和抗体的决定因素可能会指导HCV疫苗设计。在这里，作者发现新的抗HCV抗体使用计算筛选和分析的氨基酸组成和序列结构关系，在这个抗体家族。
Despite recent success in hepatitis C virus (HCV) treatment using antivirals, an HCV vaccine is still needed to prevent reinfections in treated patients, to avert the emergence of drug-resistant strains, and to provide protection for people with no access to the antiviral therapeutics. The early production of broadly neutralizing antibodies (bNAbs) associates with HCV clearance. Several potent bNAbs bind a conserved HCV glycoprotein E2 epitope using an unusual heavy chain complementarity determining region 3 (HCDR3) containing an intra-loop disulfide bond. Isolation of additional structurally-homologous bNAbs would facilitate the recognition of key determinants of such bNAbs and guide rational vaccine design. Here we report the identification of new antibodies containing an HCDR3 disulfide bond motif using computational screening with the Rosetta software. Using the newly-discovered and already-known members of this antibody family, we review the required HCDR3 amino acid composition and propose determinants for the bent versus straight HCDR3 loop conformation observed in these antibodies. Identifying determinants of broadly neutralizing antibodies against hepatitis C virus (HCV) may guide HCV vaccine design. Here, the authors discover new anti-HCV antibodies using computational screening and analyze the amino acid composition and sequence-structure relationships in this antibody family.
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影响因子：
32.4
作者：
Chen F;Tzarum N;Lin X;Giang E;Velázquez-Moctezuma R;Augestad EH;Nagy K;He L;Hernandez M;Fouch ME;Grinyó A;Chavez D;Doranz BJ;Prentoe J;Stanfield RL;Lanford R;Bukh J;Wilson IA;Zhu J;Law M
通讯作者：
Law M
影响因子：
7.7
作者：
Flyak, Andrew, I;Ruiz, Stormy E.;Bjorkman, Pamela J.
通讯作者：
Bjorkman, Pamela J.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
8
作者：
Bailey, Justin R.;Flyak, Andrew I.;Crowe, James E., Jr.
通讯作者：
Crowe, James E., Jr.
影响因子：
32.4
作者：
Goodwin E;Gilman MSA;Wrapp D;Chen M;Ngwuta JO;Moin SM;Bai P;Sivasubramanian A;Connor RI;Wright PF;Graham BS;McLellan JS;Walker LM
通讯作者：
Walker LM