Using accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein

Evandro Chagas Institute, Federal University of Pará, Federal Institute of Education, Science and Technology of Pará, FAPESPA and CNPq.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil / Universidade Federal do Pará. Instituto de Ciências Exatas e Naturais. Laboratório de Planejamento e Desenvolvimento de Fármacos. Belém, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Federal Institute of Education, Science and Technology of Pará. Tucuruí, PA, Brazil.Federal Institute of Education, Science and Technology of Pará. Tucuruí, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Exatas e Naturais. Laboratório de Planejamento e Desenvolvimento de Fármacos. Belém, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.The envelope (E) protein is an important target for antibodies in favivirus. Literature reports that the mutation T198F, located at the domain I-II hinge of the E protein, regulates viral breathing and increases the accessibility of a distal cryptic epitope located on the fusion loop, having a direct impact in the neutralization of West Nile virus (WNV). Our study aimed to describe, using accelerated molecular dynamics simulations, the efects of the T198F mutation in the fexibility of the E protein of WNV and to elucidate the mechanism that regulates epitope accessibility. The simulation results revealed that the mutation favors the formation of alternative hydrogen bonds, hampering the bending movement between domains I and II. We hypothesized that this is the mechanism by which the T198F mutation, located at the middle of the protein, locks the distal cryptc epitope near a single preferred conformation, rendering it more prone to recognition by antibodies

Genomic epidemiology reveals how restriction measures shaped the SARS-CoV-2 epidemic in Brazil

Abstract Brazil has experienced some of the highest numbers of COVID-19 infections and deaths globally and made Latin America a pandemic epicenter from May 2021. Although SARS-CoV-2 established sustained transmission in Brazil early in the pandemic, important gaps remain in our understanding of local virus transmission dynamics. Here, we describe the genomic epidemiology of SARS-CoV-2 using near-full genomes sampled from 27 Brazilian states and an adjacent country - Paraguay. We show that the early stage of the pandemic in Brazil was characterised by the co-circulation of multiple viral lineages, linked to multiple importations predominantly from Europe, and subsequently characterized by large local transmission clusters. As the epidemic progressed, the absence of effective restriction measures led to the local emergence and international spread of Variants of Concern (VOC) and under monitoring (VUM), including the Gamma (P.1) and Zeta (P.2) variants. In addition, we provide a preliminary genomic overview of the epidemic in Paraguay, showing evidence of importation from Brazil. These data reinforce the need for the implementation of widespread genomic surveillance in South America as a toolkit for pandemic monitoring and providing a means to follow the real-time spread of emerging SARS-CoV-2 variants with possible implications for public health and immunization strategies