ABSTRACT
Host genetic susceptibility is a key risk factor for severe illness associated with COVID-19. Despite numerous studies of COVID-19 host genetics, our knowledge of COVID-19-associated variants is still limited, and there is no resource comprising all the published variants and categorizing them based on their confidence level. Also, there are currently no computational tools available to predict novel COVID-19 severity variants. Therefore, we collated 820 host genetic variants reported to affect COVID-19 susceptibility by means of a systematic literature search and confidence evaluation, and obtained 196 high-confidence variants. We then developed the first machine learning classifier of severe COVID-19 variants to perform a genome-wide prediction of COVID-19 severity for 82,468,698 missense variants in the human genome. We further evaluated the classifier's predictions using feature importance analyses to investigate the biological properties of COVID-19 susceptibility variants, which identified conservation scores as the most impactful predictive features. The results of enrichment analyses revealed that genes carrying high-confidence COVID-19 susceptibility variants shared pathways, networks, diseases and biological functions, with the immune system and infectious disease being the most significant categories. Additionally, we investigated the pleiotropic effects of COVID-19-associated variants using phenome-wide association studies (PheWAS) in ~40,000 BioMe BioBank genotyped individuals, revealing pre-existing conditions that could serve to increase the risk of severe COVID-19 such as chronic liver disease and thromboembolism. Lastly, we generated a web-based interface for exploring, downloading and submitting genetic variants associated with COVID-19 susceptibility for use in both research and clinical settings (https://itanlab.shinyapps.io/COVID19webpage/). Taken together, our work provides the most comprehensive COVID-19 host genetics knowledgebase to date for the known and predicted genetic determinants of severe COVID-19, a resource that should further contribute to our understanding of the biology underlying COVID-19 susceptibility and facilitate the identification of individuals at high risk for severe COVID-19.Copyright © 2023 Elsevier Inc.
ABSTRACT
COVID-19 is a disease caused by the SARS-CoV-2 virus and represents one of the greatest health problems that humanity faces at the moment. Therefore, efforts have been made with the objective of seeking therapies that could be effective in combating this problematic. In the search for ligands, computational chemistry plays an essential role, since it allows the screening of thousands of molecules on a given target, in order to save time and money for the in vitro or in vivo pharmacological stage. In this paper, we perform a virtual screening by docking looking for potential inhibitors of the NSP16-NSP10 protein dimer (methyltransferase) from SARS-CoV-2, by evaluating a homemade databank of molecules found in plants of the Caatinga Brazilian biome, compounds from ZINC online molecular database, as well as structural analogues of the enzymatic cofactor s-adenosylmethionine (SAM) and a known inhibitor in the literature, sinefungin (SFG), provided at PubChem database. All the evaluated sets presented molecules that deserve attention, highlighting four compounds from ZINC as the most promising ligands. These results contribute to the discovery of new molecular hits, in the search of potential agents against SARS-CoV-2 virus, still unveiling a pathway that can be used in combined therapies.
ABSTRACT
The coronavirus disease 2019 (COVID-19) is still spreading fast in several tropical countries after more than one year of pandemic. In this scenario, the effects of weather conditions that can influence the spread of the virus are not clearly understood. This study aimed to analyse the influence of meteorological (temperature, wind speed, humidity and specific enthalpy) and human mobility variables in six cities (Barranquilla, Bogota, Cali, Cartagena, Leticia and Medellin) from different biomes in Colombia on the coronavirus dissemination from March 25, 2020, to January 15, 2021. Rank correlation tests and a neural network named self-organising map (SOM) were used to investigate similarities in the dynamics of the disease in the cities and check possible relationships among the variables. Two periods were analysed (quarantine and post-quarantine) for all cities together and individually. The data were classified in seven groups based on city, date and biome using SOM. The virus transmission was most affected by mobility variables, especially in the post-quarantine. The meteorological variables presented different behaviours on the virus transmission in different biogeographical regions. The wind speed was one of the factors connected with the highest contamination rate recorded in Leticia. The highest new daily cases were recorded in Bogota where cold/dry conditions (average temperature <14 °C and absolute humidity >9 g/m3) favoured the contagions. In contrast, Barranquilla, Cartagena and Leticia presented an opposite trend, especially with the absolute humidity >22 g/m3. The results support the implementation of better local control measures based on the particularities of tropical regions.