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Genomic recombination is an important driving force for viral evolution, and recombination events have been reported for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the Coronavirus Disease 2019 pandemic, which significantly alter viral infectivity and transmissibility. However, it is difficult to identify viral recombination, especially for low-divergence viruses such as SARS-CoV-2, since it is hard to distinguish recombination from in situ mutation. Herein, we applied information theory to viral recombination analysis and developed VirusRecom, a program for efficiently screening recombination events on viral genome. In principle, we considered a recombination event as a transmission process of ''information'' and introduced weighted information content (WIC) to quantify the contribution of recombination to a certain region on viral genome; then, we identified the recombination regions by comparing WICs of different regions. In the benchmark using simulated data, VirusRecom showed a good balance between precision and recall compared to two competing tools, RDP5 and 3SEQ. In the detection of SARS-CoV-2 XE, XD and XF recombinants, VirusRecom providing more accurate positions of recombination regions than RDP5 and 3SEQ. In addition, we encapsulated the VirusRecom program into a command-line-interface software for convenient operation by users. In summary, we developed a novel approach based on information theory to identify viral recombination within highly similar sequences, providing a useful tool for monitoring viral evolution and epidemic control. [ABSTRACT FROM AUTHOR]

The variety and widespread of coronavirus in natural reservoir animals is likely to cause epidemics via interspecific transmission, which has attracted much attention due to frequent coronavirus epidemics in recent decades. Birds are natural reservoir of various viruses, but the existence of coronaviruses in wild birds in central China has been barely studied. Some bird coronaviruses belong to the genus of Deltacoronavirus. To explore the diversity of bird deltacoronaviruses in central China, we tested faecal samples from 415 wild birds in Hunan Province, China. By RT‐PCR detection, we identified eight samples positive for deltacoronaviruses which were all from common magpies, and in four of them, we successfully amplified complete deltacoronavirus genomes distinct from currently known deltacoronavirus, indicating four novel deltacoronavirus stains (HNU1‐1, HNU1‐2, HNU2 and HNU3). Comparative analysis on the four genomic sequences showed that these novel magpie deltacoronaviruses shared three different S genes among which the S genes of HNU1‐1 and HNU1‐2 showed 93.8% amino acid (aa) identity to that of thrush coronavirus HKU12, HNU2 S showed 71.9% aa identity to that of White‐eye coronavirus HKU16, and HNU3 S showed 72.4% aa identity to that of sparrow coronavirus HKU17. Recombination analysis showed that frequent recombination events of the S genes occurred among these deltacoronavirus strains. Two novel putative cleavage sites separating the non‐structural proteins in the HNU coronaviruses were found. Bayesian phylogeographic analysis showed that the south coast of China might be a potential origin of bird deltacoronaviruses existing in inland China. In summary, these results suggest that common magpie in China carries diverse deltacoronaviruses with novel genomic features, indicating an important source of environmental coronaviruses closed to human communities, which may provide key information for prevention and control of future coronavirus epidemics. [ABSTRACT FROM AUTHOR]

Coronavirus (CoV) pandemics have become a huge threat to the public health worldwide in the recent decades. Typically, severe acute respiratory syndrome CoV (SARS‐CoV) caused SARS pandemic in 2003 and SARS‐CoV‐2 caused the ongoing COVID‐19 pandemic. Both viruses are most likely originated from bats. Thus, direct or indirect inter‐species transmission from bats to humans is required for the viruses to cause pandemics. Receptor utilization is a key factor determining the host range of viruses which is critical to the inter‐species transmission. Angiotensin‐converting enzyme 2 (ACE2) is the receptor of both SARS‐CoV and SARS‐CoV‐2, but only ACE2s of certain animals can be utilized by the viruses. Here, we employed pseudovirus cell‐entry assay to evaluate the receptor‐utilizing capability of ACE2s of 20 animals by the two viruses and found that SARS‐CoV‐2 utilized less ACE2s than SARS‐CoV, indicating a narrower host range of SARS‐CoV‐2. Especially, SARS‐CoV‐2 tended not to use murine or non‐mammal ACE2s. Meanwhile, pangolin‐CoV, another SARS‐related coronavirus highly homologous to SARS‐CoV‐2 in its genome, yet showed similar ACE2 utilization profile with SARS‐CoV rather than SARS‐CoV‐2. Nevertheless, the actual susceptibility of these animals to the coronaviruses should be further verified by in vivo studies. To clarify the mechanism underlying the receptor utilization, we compared the amino acid sequences of the 20 ACE2s and found 5 amino acid residues potentially critical for ACE2 utilization, including the N‐terminal 20th and 42nd amino acid residues that might determine the different receptor utilization of SARS‐CoV, SARS‐CoV‐2 and pangolin‐CoV. Our studies enhance the understanding of receptor utilization of pandemic coronaviruses, potentially contributing to the virus tracing, intermediate host screening and epidemic prevention for pathogenic coronaviruses. [ABSTRACT FROM AUTHOR]

• BioAider is an efficient tool for high-throughput analysis of viral genomes. • BioAider monitors viral variation that facilitates epidemic control of COVID-19. • 14 substitution hotspots in SARS-CoV-2 genome indicates viral polymorphism. • NSP13-Y541C was found to be a crucial substitution key viral replication. • The unique SSRX repeats on N protein suggests the animal origin of SARS-CoV-2. The novel human coronavirus (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19) pandemic worldwide. Control of COVID-19 pandemic is vital for public health and is the prerequisite to maintain social stability. However, the origin and transmission route of SARS-CoV-2 is unclear, bringing huge difficult to virus control. Monitoring viral variation and screening functional mutation sites are crucial for prevention and control of infectious diseases. In this study, we developed a user-friendly software, named BioAider, for quick sequence annotation and mutation analysis on large-scale genome-sequencing data. Herein, we detected 14 substitution hotspots within 3,240 SARS-CoV-2 genome sequences, including 3 groups of potentially linked substitution. NSP13-Y541C was crucial substitution which might affect the unwinding activity of the viral helicase. In particular, we discovered a SR-rich region of SARS-CoV-2 distinct from SARS-CoV, indicating more complex replication mechanism and unique N-M interaction of SARS-CoV-2. Interestingly, the quantity of SSRX repeat fragments in SARS-CoV-2 provided further evidence of its animal origin. Overall, we developed an efficient tool for rapid identification of viral genome mutations which could facilitate viral genomic studies. Using this tool, we have found critical clues for the transmission route of SARS-CoV-2 which would provide theoretical support for the epidemic control of pathogenic coronaviruses. [ABSTRACT FROM AUTHOR]

• The 442th amino acid is critical for host adaption of SARS-like coronaviruses. • Substitution of Y442S in spike enhances SARS-CoV utilization of bat ACE2. • Substitution of S442Y in spike abolishes bat SARSr-CoV utilization of bat, civet and human ACE2s. • The 442th amino acid is key for the receptor binding of SARSr-CoV spike with ACE2. Bats carry diverse severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). The suspected interspecies transmission of SARSr-CoVs from bats to humans has caused two severe CoV pandemics, the SARS pandemic in 2003 and the recent COVID-19 pandemic. The receptor utilization of SARSr-CoV plays the key role in determining the host range and the interspecies transmission ability of the virus. Both SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2 (ACE2) as their receptor. Previous studies showed that WIV1 strain, the first living coronavirus isolated from bat using ACE2 as its receptor, is the prototype of SARS-CoV. The receptor-binding domain (RBD) in the spike protein (S) of SARS-CoV and WIV1 is responsible for ACE2 binding and medicates the viral entry. Comparing to SARS-CoV, WIV1 has three distinct amino acid residues (442, 472, and 487) in its RBD. This study aimed at exploring whether these three residues could alter the receptor utilization of SARSr-CoVs. We replaced the three residues in SARS-CoV (BJ01 strain) S with their counterparts in WIV1 S, and then evaluated the change of their utilization of bat, civet, and human ACE2s using a lentivirus-based pseudovirus infection system. To further validate the S-ACE2 interactions, the binding affinity between the RBDs of these S proteins and the three ACE2s were verified by flow cytometry. The results showed that the single amino acid substitution Y442S in the RBD of BJ01 S enhanced its utilization of bat ACE2 and its binding affinity to bat ACE2. On the contrary, the reverse substitution in WIV1 S (S442Y) significantly attenuated the pseudovirus utilization of bat, civet and human ACE2s for cell entry, and reduced its binding affinity with the three ACE2s. These results suggest that the S442 is critical for WIV1 adapting to bats as its natural hosts. These findings will enhance our understanding of host adaptations and cross-species infections of coronaviruses, contributing to the prediction and prevention of coronavirus epidemics. [ABSTRACT FROM AUTHOR]