用于阻断新冠病毒刺突蛋白受体结合域的潜在嵌合肽。
Potential chimeric peptides to block the SARS-CoV-2 spike receptor-binding domain.
作者信息
Barh Debmalya, Tiwari Sandeep, Silva Andrade Bruno, Giovanetti Marta, Almeida Costa Eduardo, Kumavath Ranjith, Ghosh Preetam, Góes-Neto Aristóteles, Carlos Junior Alcantara Luiz, Azevedo Vasco
机构信息
Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, WB, India.
Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
出版信息
F1000Res. 2020 Jun 9;9:576. doi: 10.12688/f1000research.24074.1. eCollection 2020.
There are no known medicines or vaccines to control the COVID-19 pandemic caused by SARS-CoV-2 (nCoV). Antiviral peptides are superior to conventional drugs and may also be effective against COVID-19. Hence, we investigated the SARS-CoV-2 Spike receptor-binding domain (nCoV-RBD) that interacts with hACE2 for viral attachment and entry. Three strategies and bioinformatics approaches were employed to design potential nCoV-RBD - hACE2 interaction-blocking peptides that may restrict viral attachment and entry. Firstly, the key residues interacting with nCoV-RBD - hACE2 are identified and hACE2 sequence-based peptides are designed. Second, peptides from five antibacterial peptide databases that block nCoV-RBD are identified; finally, a chimeric peptide design approach is used to design peptides that can bind to key nCoV-RBD residues. The final peptides are selected based on their physiochemical properties, numbers and positions of key residues binding, binding energy, and antiviral properties. We found that: (i) three amino acid stretches in hACE2 interact with nCoV-RBD; (ii) effective peptides must bind to three key positions of nCoV-RBD (Gly485/Phe486/Asn487, Gln493, and Gln498/Thr500/Asn501); (iii) Phe486, Gln493, and Asn501 are critical residues; (iv) AC20 and AC23 derived from hACE2 may block two key critical positions; (iv) DBP6 identified from databases can block the three sites of the nCoV-RBD and interacts with one critical position, Gln498; (v) seven chimeric peptides were considered promising, among which cnCoVP-3, cnCoVP-4, and cnCoVP-7 are the top three; and (vi) cnCoVP-4 meets all the criteria and is the best peptide. To conclude, using three different bioinformatics approaches, we identified 17 peptides that can potentially bind to the nCoV-RBD that interacts with hACE2. Binding these peptides to nCoV-RBD may potentially inhibit the virus to access hACE2 and thereby may prevent the infection. Out of 17, 10 peptides have promising potential and need further experimental validation.
目前尚无已知药物或疫苗可控制由严重急性呼吸综合征冠状病毒2(SARS-CoV-2,即新冠病毒)引发的新冠疫情。抗病毒肽优于传统药物,可能对新冠病毒也有效。因此,我们研究了与人类血管紧张素转换酶2(hACE2)相互作用以实现病毒附着和进入的新冠病毒刺突蛋白受体结合域(nCoV-RBD)。我们采用了三种策略和生物信息学方法来设计可能限制病毒附着和进入的潜在nCoV-RBD - hACE2相互作用阻断肽。首先,确定与nCoV-RBD - hACE2相互作用的关键残基,并设计基于hACE2序列的肽。其次,从五个抗菌肽数据库中鉴定出可阻断nCoV-RBD的肽;最后,采用嵌合肽设计方法来设计能与nCoV-RBD关键残基结合的肽。根据其理化性质、关键残基结合的数量和位置、结合能以及抗病毒特性来选择最终的肽。我们发现:(i)hACE2中的三个氨基酸片段与nCoV-RBD相互作用;(ii)有效的肽必须与nCoV-RBD的三个关键位置(甘氨酸485/苯丙氨酸486/天冬酰胺487、谷氨酰胺493以及谷氨酰胺498/苏氨酸500/天冬酰胺501)结合;(iii)苯丙氨酸486、谷氨酰胺493和天冬酰胺501是关键残基;(iv)源自hACE2的AC20和AC23可能阻断两个关键位置;(iv)从数据库中鉴定出的DBP6可阻断nCoV-RBD的三个位点,并与一个关键位置谷氨酰胺498相互作用;(v)七种嵌合肽被认为有前景,其中cnCoVP-3、cnCoVP-4和cnCoVP-7位列前三;(vi)cnCoVP-4符合所有标准,是最佳肽。总之,通过三种不同的生物信息学方法,我们鉴定出17种可能与与hACE2相互作用的nCoV-RBD结合的肽。使这些肽与nCoV-RBD结合可能会抑制病毒与hACE2结合,从而预防感染。17种肽中有10种具有潜在前景,需要进一步的实验验证。