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Since the beginning of the pandemic, the generation of new variants periodically recurs. The XBB.1.5 SARS-CoV-2 variant is one of the most recent. This research was aimed at verifying the potential hazard of this new subvariant. To achieve this objective, we performed a genome-based integrative approach, integrating results from genetic variability/phylodynamics with structural and immunoinformatic analyses to obtain as comprehensive a viewpoint as possible. The Bayesian Skyline Plot (BSP) shows that the viral population size reached the plateau phase on 24 November 2022, and the number of lineages peaked at the same time. The evolutionary rate is relatively low, amounting to 6.9 × 10−4 subs/sites/years. The NTD domain is identical for XBB.1 and XBB.1.5 whereas their RBDs only differ for the mutations at position 486, where the Phe (in the original Wuhan) is replaced by a Ser in XBB and XBB.1, and by a Pro in XBB.1.5. The variant XBB.1.5 seems to spread more slowly than sub-variants that have caused concerns in 2022. The multidisciplinary molecular in-depth analyses on XBB.1.5 performed here does not provide evidence for a particularly high risk of viral expansion. Results indicate that XBB.1.5 does not possess features to become a new, global, public health threat. As of now, in its current molecular make-up, XBB.1.5 does not represent the most dangerous variant. [ABSTRACT FROM AUTHOR]

The ongoing discussion about the real origin of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) feeds acrimonious debates. Where did SARS‐CoV‐2 come from? Was SARS‐CoV‐2 transmitted in the wild from an animal to a person before exploding in Wuhan or was it an engineered virus that escaped from research or a laboratory in Wuhan? Right now, we still don't know enough whether SARS‐CoV‐2 is human‐made or not, and lab‐leak theories remain essentially speculative. Many recent studies have pointed out several plausible scenarios. Anyhow, currently, even if suspicions by some about the possibility of lab‐leak hypothesis still remain, the consensus view is that the pandemic probably started from a natural source and, to determine the real origin of the SARS‐CoV‐2 virus, further research is needed. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) originated in Wuhan, China in early December 2019 has rapidly widespread worldwide. Over the course of the pandemic, due to the advance of whole‐genome sequencing technologies, an unprecedented number of genomes have been generated, providing both invaluable insights into the ongoing evolution and epidemiology of the virus and allowing the identification of hundreds of circulating genetic variants during the pandemic. In recent months variants of SARS‐CoV‐2 that have an increased number of mutations on the Spike protein have brought concern all over the world. These have been called "variants of concerns" (VOCs), and/or "variants of interests" (VOIs) as it has been suggested that their genome mutations might impact transmission, immune control, and virulence. Tracking the spread of emerging SARS‐CoV‐2 variants is crucial to inform public health efforts and control the ongoing pandemic. In this review, a concise characterization of the SARS‐CoV‐2 mutational patterns of the main VOCs and VOIs circulating and cocirculating worldwide has been presented to determine the magnitude of the SARS‐CoV‐2 threat to better understand the virus genetic diversity and its potential impact on vaccination strategy. Highlights: Over the course of the pandemic an unprecedented number of SARS‐CoV‐2 genomes have been generated.Genomic monitoring allowed the identification of "variants of concerns" (VOCs), and/or "variants of interests" (VOIs) wordlwide.Tracking the spread of emerging SARS‐CoV‐2 variants is crucial to control the ongoing pandemic. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China, in early December 2019 has rapidly widespread worldwide, becoming one of the major global public health issues of the last centuries. Key Messages: Over the course of the pandemic, due to the advanced whole-genome sequencing technologies, an unprecedented amount of genomes have been generated, providing invaluable insights into the ongoing evolution and epidemiology of the virus during the pandemic. Therefore, this large amount of data played an important role in the SARS-CoV-2 mitigation and control strategies. Key Messages: The active monitoring and characterization of the SARS-CoV-2 lineages circulating worldwide is useful for a more specific diagnosis, better care, and timely treatment. In this review, a concise characterization of all the lineages and sub-lineages circulating and co-circulating across the world has been presented in order to determine the magnitude of the SARS-CoV-2 threat and to better understand the virus genetic diversity and its dispersion dynamics. [ABSTRACT FROM AUTHOR]

Viruses arise through cross-species transmission and can cause potentially fatal diseases in humans. This is the case of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which recently appeared in Wuhan, China, and rapidly spread worldwide, causing the outbreak of coronavirus disease 2019 (COVID-19) and posing a global health emergency. Sequence analysis and epidemiological investigations suggest that the most likely original source of SARS-CoV-2 is a spillover from an animal reservoir, probably bats, that infected humans either directly or through intermediate animal hosts. The role of animals as reservoirs and natural hosts in SARS-CoV-2 has to be explored, and animal models for COVID-19 are needed as well to be evaluated for countermeasures against SARS-CoV-2 infection. Experimental cells, tissues, and animal models that are currently being used and developed in COVID-19 research will be presented. [ABSTRACT FROM AUTHOR]

Last December 2019, a new virus, named novel Coronavirus (COVID‐2019) causing many cases of severe pneumonia was reported in Wuhan, China. The virus knowledge is limited and especially about COVID‐2019 pathogenesis. The Open Reading Frame 1ab (ORF1ab) of COVID‐2019 has been analyzed to evidence the presence of mutation caused by selective pressure on the virus. For selective pressure analysis fast‐unconstrained Bayesian approximation (FUBAR) was used. Homology modelling has been performed by SwissModel and HHPred servers. The presence of transmembrane helical segments in Coronavirus ORF1ab non structural protein 2 (nsp2) and nsp3 was tested by TMHMM, MEMSAT, and MEMPACK tools. Three‐dimensional structures have been analyzed and displayed using PyMOL. FUBAR analysis revealed the presence of potential sites under positive selective pressure (P <.05). Position 723 in the COVID‐2019 has a serine instead a glycine residue, while at aminoacidic position 1010 a proline instead an isoleucine. Significant (P <.05) pervasive negative selection in 2416 sites (55%) was found. The positive selective pressure could account for some clinical features of this virus compared with severe acute respiratory syndrome (SARS) and Bat SARS‐like CoV. The stabilizing mutation falling in the endosome‐associated‐protein‐like domain of the nsp2 protein could account for COVID‐2019 high ability of contagious, while the destabilizing mutation in nsp3 proteins could suggest a potential mechanism differentiating COVID‐2019 from SARS. These data could be helpful for further investigation aimed to identify potential therapeutic targets or vaccine strategy, especially in the actual moment when the epidemic is ongoing and the scientific community is trying to enrich knowledge about this new viral pathogen. Highlights: Analysis of selective pressure on COVID‐19 ORF1ab has been analyzed.Aminoacid position 501, 723 and 1010 have changed than SARs virus and Bat‐SARS‐like coronaviirus.Stabilizing mutation at nsp2 protein could explain why COVID‐19 is more contagious than SARS.Destabilizing mutaion of nsp3 protein could explain the difference oberved between SARS and COVID‐19. [ABSTRACT FROM AUTHOR]

A novel Coronavirus, 2019‐nCoV, has been identified as the causal pathogen of an ongoing epidemic, with the first cases reported in Wuhan, China, last December 2019, and has since spread to other countries worldwide, included Europe and very recently Italy. In this short report, phylogenetic reconstruction was used to better understand the transmission dynamics of the virus from its first introduction in China focusing on the more recent evidence of infection in a couple of Chinese tourists arrived in Italy on 23rd January 2020 and labeled as Coronavirus Italian cases. A maximum clade credibility tree has been built using a dataset of 54 genome sequences of 2019‐nCoV plus two closely related bat strains (SARS‐like CoV) available in GenBank. Bayesian time‐scaled phylogenetic analysis was implemented in BEAST 1.10.4. The Bayesian phylogenetic reconstruction showed that 2019‐2020 nCoV firstly introduced in Wuhan on 25 November 2019, started epidemic transmission reaching many countries worldwide, including Europe and Italy where the two strains isolated dated back 19 January 2020, the same that the Chinese tourists arrived in Italy. Strains isolated outside China were intermixed with strains isolated in China as evidence of likely imported cases in Rome, Italy, and Europe, as well. In conclusion, this report suggests that further spread of 2019‐nCoV epidemic was supported by human mobility and that quarantine of suspected or diagnosed cases is useful to prevent further transmission. Viral genome phylogenetic analysis represents a useful tool for the evaluation of transmission dynamics and preventive action. Highlights: The 2019‐nCoV epidemic is representing a global public health concern.In this short report phylogenetic analysis was used to trace and date the origin of infection in the first two cases of 201‐nCoV registered in Italy.The phylogenetic tree clearly showed that the two sequences clustered together in a supported clade with other sequence from China.The infection was dated some days before tourist arrival in Italy.The two first cases of 2019‐nCoV isolated in Italy can be reasonable labeled as imported cases from China.Phylogenetic analysis represents a valid tool for the evaluation of transmission dynamics and preventive actions. [ABSTRACT FROM AUTHOR]

There is a worldwide concern about the new coronavirus 2019‐nCoV as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. A phylogenetic tree has been built using the 15 available whole genome sequences of 2019‐nCoV, 12 whole genome sequences of 2019‐nCoV, and 12 highly similar whole genome sequences available in gene bank (five from the severe acute respiratory syndrome, two from Middle East respiratory syndrome, and five from bat SARS‐like coronavirus). Fast unconstrained Bayesian approximation analysis shows that the nucleocapsid and the spike glycoprotein have some sites under positive pressure, whereas homology modeling revealed some molecular and structural differences between the viruses. The phylogenetic tree showed that 2019‐nCoV significantly clustered with bat SARS‐like coronavirus sequence isolated in 2015, whereas structural analysis revealed mutation in Spike Glycoprotein and nucleocapsid protein. From these results, the new 2019‐nCoV is distinct from SARS virus, probably trasmitted from bats after mutation conferring ability to infect humans. Highlights: An epidemic by a new Coronavirus, the 2019‐nCoV is worrying worldwide.The epdiemic originated in Wuhan, China causing severe infections in some cases.The infection probably originated in bats.A mutation in the viral spike glycoprotein could have favured the cross‐sepcies tramsnimssion from bats to human. [ABSTRACT FROM AUTHOR]

Background: The new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first detected in Wuhan (China) in December of 2019 is responsible for the current global pandemic. Phylogenetic analysis revealed that it is similar to other betacoronaviruses, such as SARS-CoV and Middle-Eastern Respiratory Syndrome, MERS-CoV. Its genome is ∼ 30 kb in length and contains two large overlapping polyproteins, ORF1a and ORF1ab that encode for several structural and non-structural proteins. The non-structural protein 1 (nsp1) is arguably the most important pathogenic determinant, and previous studies on SARS-CoV indicate that it is both involved in viral replication and hampering the innate immune system response. Detailed experiments of site-specific mutagenesis and in vitro reconstitution studies determined that the mechanisms of action are mediated by (a) the presence of specific amino acid residues of nsp1 and (b) the interaction between the protein and the host's small ribosomal unit. In fact, substitution of certain amino acids resulted in reduction of its negative effects.Methods: A total of 17,928 genome sequences were obtained from the GISAID database (December 2019 to July 2020) from patients infected by SARS-CoV-2 from different areas around the world. Genomes alignment was performed using MAFFT (REFF) and the nsp1 genomic regions were identified using BioEdit and verified using BLAST. Nsp1 protein of SARS-CoV-2 with and without deletion have been subsequently modelled using I-TASSER.Results: We identified SARS-CoV-2 genome sequences, from several Countries, carrying a previously unknown deletion of 9 nucleotides in position 686-694, corresponding to the AA position 241-243 (KSF). This deletion was found in different geographical areas. Structural prediction modelling suggests an effect on the C-terminal tail structure.Conclusions: Modelling analysis of a newly identified deletion of 3 amino acids (KSF) of SARS-CoV-2 nsp1 suggests that this deletion could affect the structure of the C-terminal region of the protein, important for regulation of viral replication and negative effect on host's gene expression. In addition, substitution of the two amino acids (KS) from nsp1 of SARS-CoV was previously reported to revert loss of interferon-alpha expression. The deletion that we describe indicates that SARS-CoV-2 is undergoing profound genomic changes. It is important to: (i) confirm the spreading of this particular viral strain, and potentially of strains with other deletions in the nsp1 protein, both in the population of asymptomatic and pauci-symptomatic subjects, and (ii) correlate these changes in nsp1 with potential decreased viral pathogenicity. [ABSTRACT FROM AUTHOR]