ABSTRACT
Coronavirus disease-2019 (COVID-19) is an infectious disease caused by SARS-CoV-2 virus. The microbes inhabiting the oral cavity and gut might play crucial roles in maintaining a favorable gut environment, and their relationship with SARS-CoV-2 infection susceptibility and severity is yet to be fully explored. This study investigates the diversity and species richness of gut and oral microbiota of patients with COVID-19, and their possible implications toward the severity of the patient's illness and clinical outcomes. Seventy-four (n = 74) clinical samples (gut and oral) were collected from 22 hospitalized patients with COVID-19 with various clinical conditions and 15 apparently healthy people (served as controls). This amplicon-based metagenomic sequencing study yielded 1,866,306 paired-end reads that were mapped to 21 phyla and 231 classified genera of bacteria. Alpha and beta diversity analyses revealed a distinct dysbiosis of the gut and oral microbial communities in patients with COVID-19, compared to healthy controls. We report that SARS-CoV-2 infection significantly reduced richness and evenness in the gut and oral microbiomes despite showing higher unique operational taxonomic units in the gut. The gut samples of the patients with COVID-19 included 46 opportunistic bacterial genera. Escherichia, Shigella, and Bacteroides were detected as the signature genera in the gut of patients with COVID-19 with diarrhea, whereas a relatively higher abundance of Streptococcus was found in patients with COVID-19 having breathing difficulties and sore throat (BDST). The patients with COVID-19 had a significantly lower abundance of Prevotella in the oral cavity, compared to healthy controls and patients with COVID-19 without diabetes, respectively. The altered metabolic pathways, including a reduction in biosynthesis capabilities of the gut and oral microbial consortia after SARS-CoV-2 infection, were also observed. The present study may, therefore, shed light on interactions of SARS-CoV-2 with resilient oral and gut microbes which might contribute toward developing microbiome-based diagnostics and therapeutics for this deadly pandemic disease.
ABSTRACT
The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected in S, 12 variations were located at the N-terminal domain (NTD) and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin-converting enzyme 2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.