"Mutation blacklist" and "mutation whitelist" of SARS-CoV-2.

Over the past two years, scientists throughout the world have completed more than 6 million SARS-CoV-2 genome sequences. Today, the number of SARS-CoV-2 genomes exceeds the total number of all other viral genomes. These genomes are a record of the evolution of SARS-CoV-2 in the human host, and provide information on the emergence of mutations. In this study, analysis of these sequenced genomes identified 296,728 de novo mutations (DNMs), and found that six types of base substitutions reached saturation in the sequenced genome population. Based on this analysis, a "mutation blacklist" of SARS-CoV-2 was compiled. The loci on the "mutation blacklist" are highly conserved, and these mutations likely have detrimental effects on virus survival, replication, and transmission. This information is valuable for SARS-CoV-2 research on gene function, vaccine design, and drug development. Through association analysis of DNMs and viral transmission rates, we identified 185 DNMs that positively correlated with the SARS-CoV-2 transmission rate, and these DNMs where classified as the "mutation whitelist" of SARS-CoV-2. The mutations on the "mutation whitelist" are beneficial for SARS-CoV-2 transmission and could therefore be used to evaluate the transmissibility of new variants. The occurrence of mutations and the evolution of viruses are dynamic processes. To more effectively monitor the mutations and variants of SARS-CoV-2, we built a SARS-CoV-2 mutation and variant monitoring and pre-warning system (MVMPS), which can monitor the occurrence and development of mutations and variants of SARS-CoV-2, as well as provide pre-warning for the prevention and control of SARS-CoV-2 (https://www.omicx.cn/). Additionally, this system could be used in real-time to update the "mutation whitelist" and "mutation blacklist" of SARS-CoV-2.

The Threat of Potentially Pathogenic Bacteria in the Feces of Bats.

Bats have attracted global attention because of their zoonotic association with severe acute respiratory syndrome coronavirus (SARS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Previous and ongoing studies have predominantly focused on bat-borne viruses; however, the prevalence or abundance of bat-borne pathogenic bacteria and their potential public health significance have largely been neglected. For the first time, this study used both metataxonomics (16S rRNA marker gene sequencing) and culturomics (traditional culture methods) to systematically evaluate the potential public health significance of bat fecal pathogenic bacteria. To this end, fecal samples were obtained from five bat species across different locations in China, and their microbiota composition was analyzed. The results revealed that the bat microbiome was most commonly dominated by Proteobacteria, while the strictly anaerobic phylum Bacteroidetes occupied 35.3% of the relative abundance in Rousettus spp. and 36.3% in Hipposideros spp., but less than 2.7% in the other three bat species (Taphozous spp., Rhinolophus spp., and Myotis spp.). We detected 480 species-level phylotypes (SLPs) with PacBio sequencing, including 89 known species, 330 potentially new species, and 61 potentially higher taxa. In addition, a total of 325 species were identified by culturomics, and these were classified into 242 named species and 83 potentially novel species. Of note, 32 of the 89 (36.0%) known species revealed by PacBio sequencing were found to be pathogenic bacteria, and 69 of the 242 (28.5%) known species isolated by culturomics were harmful to people, animals, or plants. Additionally, nearly 40 potential novel species which may be potential bacterial pathogens were identified. IMPORTANCE Bats are one of the most diverse and widely distributed groups of mammals living in close proximity to humans. In recent years, bat-borne viruses and the viral zoonotic diseases associated with bats have been studied in great detail. However, the prevalence and abundance of pathogenic bacteria in bats have been largely ignored. This study used high-throughput sequencing techniques (metataxonomics) in combination with traditional culture methods (culturomics) to analyze the bacterial flora in bat feces from different species of bats in China, revealing that bats are natural hosts of pathogenic bacteria and carry many unknown bacteria. The results of this study can be used as guidance for future investigations of bacterial pathogens in bats.

Evolutionary analysis of Omicron variant BF.7 and BA.5.2 pandemic in China.

On December 7, 2022, China adjusted public health control measures, there have been widespread of SARS-CoV-2 infections in Chinese mainland. As the number of infected people increased, the mutation probability of SARS-CoV-2 is also raised. Therefore, it is of great importance to monitor SARS-CoV-2 variants and its mutations in China. In this current study, 665 SARS-CoV-2 genomes from China deposited in the public database were used to analyze the proportion of different variants; to determine the composition of variants in China across different provinces; and analyze specific mutation frequency, focusing on 12 immune escape residues. The results showed that no new mutations were generated on the 12 immune escape residues. The evolutionary analysis of the BF.7 variant circulating in China showed that there is an independent evolutionary branch with unique mutation sites, officially named BF.7.14 by PANGO. This variant may have been imported from Russia to Inner Mongolia at the end of September 2022 and continued its spread in China. The evolutionary analysis of BA.5.2 variant shows that the variant is composed of two sub-variants, named BA.5.2.48 and BA.5.2.49 by PANGO, respectively. This variant may have been imported from abroad to Beijing at the beginning of September 2022 and formed two sub-variants after domestic transmission. Finally, this study showed that current epidemic variants in China were already circulating in other countries, and there were no additional mutations on immune escape residues that could pose a threat to other countries.

Massive‐scale genomic analysis reveals SARS‐CoV‐2 mutation characteristics and evolutionary trends

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic resulted in significant societal costs. Hence, an in‐depth understanding of SARS‐CoV‐2 virus mutation and its evolution will help determine the direction of the COVID‐19 pandemic. In this study, we identified 296,728 de novo mutations in more than 2,800,000 high‐quality SARS‐CoV‐2 genomes. All possible factors affecting the mutation frequency of SARS‐CoV‐2 in human hosts were analyzed, including zinc finger antiviral proteins, sequence context, amino acid change, and translation efficiency. As a result, we proposed that when adenine (A) and tyrosine (T) bases are in the context of AM (M stands for adenine or cytosine) or TA motif, A or T base has lower mutation frequency. Furthermore, we hypothesized that translation efficiency can affect the mutation frequency of the third position of the codon by the selection, which explains why SARS‐CoV‐2 prefers AT3 codons usage. In addition, we found a host‐specific asymmetric dinucleotide mutation frequency in the SARS‐CoV‐2 genome, which provides a new basis for determining the origin of the SARS‐CoV‐2. Finally, we summarize all possible factors affecting mutation frequency and provide insights into the mutation characteristics and evolutionary trends of SARS‐CoV‐2. Impact statement In this study, we analyzed the possible factors affecting mutations in more than 2,800,000 high‐quality severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) genomes. To our knowledge we are the first to propose that when the A or T base conforms to AM or TA motif, the A or T base has a lower mutation frequency;and subsequently, translation efficiency can affect the mutation frequency from C/G to A/T on the third position of the codon by the selection. We found significant host‐specific asymmetric mutations at dinucleotide sites. In addition, we also identified the characteristics of SARS‐CoV‐2 mutations and hypothesized the evolutionary trends of the virus in the human host. These findings are valuable for predicting the development of the COVID‐19 pandemic and bring to light new hypotheses regarding the origin of SARS‐CoV‐2.

Origin and evolutionary analysis of the SARS-CoV-2 Omicron variant.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved rapidly into new variants throughout the pandemic. The Omicron variant has more than 50 mutations when compared with the original wild-type strain and has been identified globally in numerous countries. In this report, we analyzed the mutational profiles of several variants, including the per-site mutation rate, to determine evolutionary relationships. The Omicron variant was found to have a unique mutation profile when compared with that of other SARS-CoV-2 variants, containing mutations that are rare in clinical samples. Moreover, the presence of five mouse-adapted mutation sites suggests that Omicron may have evolved in a mouse host. Mutations in the Omicron receptor-binding domain (RBD) region, in particular, have potential implications for the ongoing pandemic.