SARS-CoV-2: An Update on Genomics, Risk Assessment, Potential Therapeutics and Vaccine Development

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great threat to public health, being a causative pathogen of a deadly coronavirus disease (COVID-19). It has spread to more than 200 countries and infected millions of individuals globally. Although SARS-CoV-2 has structural/genomic similarities with the previously reported SARS-CoV and MERS-CoV, the specific mutations in its genome make it a novel virus. Available therapeutic strategies failed to control this virus. Despite strict standard operating procedures (SOPs), SARS-CoV-2 has spread globally and it is mutating gradually as well. Diligent efforts, special care, and awareness are needed to reduce transmission among susceptible masses particularly elder people, children, and health care workers. In this review, we highlighted the basic genome organization and structure of SARS-CoV-2. Its transmission dynamics, symptoms, and associated risk factors are discussed. This review also presents the latest mutations identified in its genome, the potential therapeutic options being used, and a brief explanation of vaccine development efforts against COVID-19. The effort will not only help readers to understand the deadly SARS-CoV-2 virus but also provide updated information to researchers for their research work.

SARS-CoV-2 Vaccines Based on the Spike Glycoprotein and Implications of New Viral Variants

“…The Federal Budgetary Research Institution State Research Center of Virology and Biotechnology Russia “Vector” has designed a peptide vaccine conjugated to a recombinant carrier protein and adsorbed on aluminum hydroxide. Synthetic peptides include: 403-RGDEVRQIAPGQTGKIADYNYKLPDD-248, 454-RLFRKSNLKPFERDISTEIYQAGS-477, 627-DQLTPTWRVYSTGSNVFQTR-646, 1192-NLNESLIDLQELGKYEQYIK-1211 and 1181-KEIDRLNEVAKNLNESLIDLQELGKYEQYIK-1211 of the SARS-CoV-2 S glycoprotein (RU0002738081), which are approved for use in Russia ( 111 – 113 ) ( Figure 3 ).…”

“…UB-612 is another vaccine based on epitopes. This vaccine was developed for COVAXX/United Biomedical Inc. from Asia and is currently in phase 2 clinical trials ( 111 ). It is based on the S1-RBD peptides but incorporates cytotoxic T-lymphocyte (CTL)/Th epitopes which bind to human major histocompatibility complexes (MHC)-I and MHC-II for T-cell activation, respectively ( 114 , 115 ).…”

Mecanismos fisiopatológicos relacionados con la infección por SARS-CoV-2 en las personas expuestas durante 2019 y 2020.

“…El genoma de SARS-CoV-2 está compuesto por 29.891 nucleótidos que codifican para 9860 aminoácidos (6), correspondientes a dos poliproteínas (pp1a y pp1a/b), clivadas en 15/16 proteínas no estructurales (nsps) por acción de dos proteasas virales (proteasa tipo 3C o 3CLpro y proteasa tipo papaína o PLpro). Entre las nsps se incluye la polimerasa ARN dependiente de ARN (RdRp), que conforman el complejo de replicación (20,26,59). Lo anterior seguido de, al menos, 13 marcos de lectura abiertos (ORF): glucoproteína de superficie, ORF3a, ORF3b, envoltura, membrana, ORF6, ORF 7a, ORF7b, ORF8, nucleocápside, ORF9a, ORF9b y ORF10 (8,26,36,38), entre los cuales se encuentran secuencias reguladoras de la transcripción (6).…”

“…En relación con otros CoV, el genoma de SARS-CoV-2 comparte una identidad del 80 % con SARS-CoV, del 85 % con bat-SL-CoVZC45, del 89 % con bat-SL-CoVZXC21 y del 96 % con bat-CoV-RaTG13 (3,6,27,31,35). La proteína N de SARS-CoV-2 se conserva en un 90 % con respecto a la de SARS-CoV, así como la subunidad S2 de la proteína S comparte un 99 % de similitud con SARS-CoV, bat-SL-CoVZXC21 y bat-SL-CoVZC45 (27,59). En cuanto al dominio de unión al receptor (RBD) de la proteína S, SARS-CoV-2 y SARS-CoV difieren en 5 de 6 residuos (38).…”

“…Por otra parte, S2 contiene un péptido fusión (FP), heptadas repetitivas 1 y 2 (HR1 y HR2), un dominio transmembrana (TM) y uno citoplasmático (CP) (3,61). Por lo tanto, S1 contribuye a la unión con el receptor, seguido de la fusión de la envoltura viral con la membrana endosomal de la célula huésped por acción de S2 (26,59). La subunidad S1 puede intercambiar entre dos conformaciones, un estado down, en el que es inaccesible a su receptor y, por lo tanto, sugiere un mecanismo de evasión de respuesta inmune en el huésped, y un estado up, accesible al receptor (3,30).…”