© 2021 Journal of Pharmacy & Pharmacognosy Research, 9 (6), 766-779, 2021 ISSN 0719-4250 http://jppres.com/jppres Original Article Viroinformatics investigation of B-cell epitope conserved region in SARS- CoV-2 lineage B.1.1.7 isolates originated from Indonesia to develop vaccine candidate against COVID-19 [Investigación viroinformática de la región conservada del epítopo de células B en el linaje SARS-CoV-2 B.1.1.7 aislamientos originados en Indonesia para desarrollar una vacuna candidata contra COVID-19] Arif N. M. Ansori1,2#, Reviany V. Nidom1,3*#, Muhammad K. J. Kusala1,2, Setyarina Indrasari1,3, Irine Normalina1,4, Astria N. Nidom1,3, Balqis Afifah1,3, Kartika B. Sari1,5, Nor L. Ramadhaniyah1,5, Mohammad Y. Alamudi1,3, Umi Cahyaningsih6, Kuncoro P. Santoso1,2, Heri Kuswanto5, Chairul A. Nidom1,2,3* 1Coronavirus and Vaccine Formulation Research Group, Professor Nidom Foundation, Surabaya, Indonesia. 2Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia. 3Riset AIRC Indonesia, Surabaya, Indonesia. 4Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. 5Faculty of Science and Data Analytics, Institut Teknologi Sepuluh Nopember, Surabaya, Indonesia. 6Faculty of Veterinary Medicine, IPB University, Bogor, Indonesia. #Both authors contributed equally. *E-mail: [email protected], [email protected], [email protected] Abstract Resumen Context: SARS-CoV-2, a member of family Coronaviridae and the Contexto: SARS-CoV-2, un miembro de la familia Coronaviridae y el causative agent of COVID-19, is a virus which is transmitted to human agente causante de COVID-19, es un virus que se transmite a humanos y and other mammals. otros mamíferos. Aims: To analyze the B-cell epitope conserved region and Objetivos: Analizar la región conservada del epítopo de células B y el viroinformatics-based study of the SARS-CoV-2 lineage from estudio basado en viroinformática del linaje SARS-CoV-2 de los aislados Indonesian B.1.1.7 isolates to invent a vaccine nominee for overcoming B.1.1.7 de Indonesia para inventar una vacuna candidata para superar COVID-19. COVID-19. Methods: The sequences of seven Indonesian B.1.1.7 isolates, Wuhan-Hu- Métodos: Las secuencias de siete aislamientos B.1.1.7 indonesios, el 1 isolate, and WIV04 isolate were extracted from the GISAID EpiCoV aislado Wuhan-Hu-1 y el aislado WIV04 se extrajeron de GISAID and GenBank, NCBI. MEGA X was employed to understand the EpiCoV y GenBank, NCBI. Se empleó MEGA X para comprender las transformations of amino acid in the S protein and to develop a transformaciones de aminoácidos en la proteína S y para desarrollar un molecular phylogenetic tree. The IEDB was implemented to reveal the árbol filogenético molecular. El IEDB se implementó para revelar los linear B-cell epitopes. In addition, PEP-FOLD3 web server was utilized epítopos de células B lineales. Además, se utilizó el servidor web PEP- to perform peptide modeling, while docking was performed using FOLD3 para realizar el modelado de péptidos, mientras que el PatchDock, FireDock, and the PyMOL software. Moreover, in silico acoplamiento se realizó mediante PatchDock, FireDock y el software cloning was developed by using SnapGene v.3.2.1 software. PyMOL. Además, la clonación in silico se desarrolló utilizando el Results: In this study, the changes of amino acid in all seven Indonesian software SnapGene v.3.2.1. B.1.1.7 isolates were uncovered. Furthermore, various peptides based on Resultados: En este estudio, se descubrieron los cambios de aminoácidos the B-cell epitope prediction, allergenicity prediction, toxicity prediction en los siete aislamientos de B.1.1.7 de Indonesia. Además, se from S protein to generate a vaccine contrary to SARS-CoV-2 were identificaron varios péptidos basados en la predicción del epítopo de identified. Furthermore, the development of in silico cloning using pET células B, la predicción de la alergenicidad, la predicción de la toxicidad plasmid was successfully achieved. de la proteína S para generar una vacuna contraria al SARS-CoV-2. Conclusions: This study exhibits the transformations of amino acid in Además, se logró con éxito el desarrollo de la clonación in silico Indonesian B.1.1.7 isolates, and proposes four peptides utilizando el plásmido pET. (“LTPGDSSSGWTAG”, “VRQIAPGQTGKIAD”, “ILPDPSKPSKRS”, and Conclusiones: Este estudio exhibe las transformaciones de aminoácidos “KNHTSPDVDLG”) from S protein as the candidate for a peptide-based en aislados B.1.1.7 de Indonesiay propone cuatro péptidos vaccine. However, further advance trials such as in vitro and in vivo (“LTPGDSSSGWTAG”, “VRQIAPGQTGKIAD”, “ILPDPSKPSKRS” y testing are involved for validation. “KNHTSPDVDLG”) de la proteína S como candidato para una vacuna basada en péptidos. Sin embargo, para la validación se requieren más ensayos in vitro e in vivo. Keywords: COVID-19; SARS-CoV-2; vaccine design; viroinformatics. Palabras Clave: COVID-19; SARS-CoV-2; vaccine design; viroinformatics. ARTICLE INFO Received: May 10, 2021. Received in revised form: June 3, 2021. Accepted: June 5, 2021. Available Online: June 13, 2021. _____________________________________ Ansori et al. B-cell epitope of SARS-CoV-2 and COVID-19 vaccine candidate INTRODUCTION larity shared with the genome of previous variant, SARS-CoV, is quite high, around 79.5% shared SARS-CoV-2 ranked as the seventh for the similarity (Hu et al., 2020). There are four structur- coronavirus (CoV) which has transversed the bar- al proteins which conceal this genome, they are rier between species and been able to infect hu- spike (S), nucleocapsid (N), membrane (M), and man. The virus was firstly identified in China in envelope (E) (Li et al., 2020; Ou et al., 2020; Zeng et 2019 and appeared sporadically all over China and al., 2020). In addition, several researches have in- many other nations worldwide (Harapan et al., formed that SARS-CoV-2 ties up ACE2 receptor on 2020; Rodriguez-Morales et al., 2020; Wu et al., the host cell. Furthermore, the receptor contributes 2020). As the virus spreads massively and quickly, greatly in viral entry system and closely related to it was confirmed and revealed publicly by WHO pathogenicity (Harapan et al., 2020). in March 2020 that this contagious widespread has become a pandemic. The global health and econ- Various investigation is demanded to acquire omy have suffered by this COVID-19 abrupt con- molecular epidemiological data of the novel virus tagion and rapid deployment (Astuti and Ysrafil, in Indonesia (Nidom et al., 2021). Research on mo- 2020; Huang et al., 2020). This global issue has re- lecular epidemiology is a vital instrument for ob- quired revolutionary scientific progression for serving new emerging viruses. There is an urgency deep investigations on SARS-CoV-2 concerning its to establish further studies in molecular epidemi- features, mechanism of transmission, and clinical ology to comprehend the probable consequences aspects for the sole purpose of ending this pan- of the disease (Nidom et al., 2020a; 2021). Current- demic’s catastrophic impacts (Awadasseid et al., ly, a novel SARS-CoV-2 lineage was detected on 2021; Ganesh et al., 2021). Sadly, this virus has September 2020, called B.1.1.7. A variant of this costed about 170 million people getting infected virus was initially discovered in England among a globally with more than 3.5 million global deaths. large number of new cases. Then, this variant be- To be specific, Indonesia has about 1.8 million cas- comes dominant in December 2020 in Southeast- es and around 50 thousand deaths. John Hopkins ern England. B.1.1.7 variant spreads globally and University has initiated the global data pooling rapidly including in Indonesia and as predicted in with actual time updated online to pursue the real the early of March 2021 (Duong, 2021). This virus time cases of COVID-19 in numbers and geograph- variant raises concerns recognized by neutralizing ical disbursement in which these above data are the antibodies, which may be affected leading to derived from (Dong et al., 2020). non-maximum vaccine efficacy. The coronavirus family is composed of four dif- In addition, our previous study reported the ferent genera: Alpha-, Gamma-, Beta-, and Del- four structural proteins as vaccine candidate’s de- tacoronavirus. Alphacoronavirus and Betacoronavirus velopment and revealed the antibody-dependent infect animals and humans, whereas Deltacorona- enhancement (ADE) phenomenon based on the S virus and Gammacoronavirus infect only animals protein gene sequences (Ansori et al., 2020; Nidom (Raoult et al., 2020). Similar to SARS-CoV-1 and et al., 2020b; Normalina et al., 2020). The efforts to MERS-CoV, SARS-CoV-2 also is part of Coronaviri- produce vaccines globally in resistance to SARS- dae (Betacoronavirus), a family that has formerly CoV-2 by scientists with the vaccines derived from driven the previous two epidemics (Shereen et al., its proteins turned out to be one of the most pro- 2020). Referenced in some data pools, the genome gressive kinds and the driving force of this study of SARS-CoV-2 has been recognized with around is the private sectors (Callaway, 2020). Although 30 kb nucleotides in a single-stranded positive- various countries already ongoing for the COVID- sense RNA (NC_045512.2 - GenBank, NCBI and 19 vaccination program (Nidom et al., 2021), cur- EPI_ISL_402124 - GISAID EpiCoV) and the simi- rently there are no approved drugs against the virus (Harisna et al., 2021). A recent study revea- http://jppres.com/jppres J Pharm Pharmacogn Res