Identifying and prioritizing potential human-infecting viruses from their genome sequences.

Determining which animal viruses may be capable of infecting humans is currently intractable at the time of their discovery, precluding prioritization of high-risk viruses for early investigation and outbreak preparedness. Given the increasing use of genomics in virus discovery and the otherwise sparse knowledge of the biology of newly discovered viruses, we developed machine learning models that identify candidate zoonoses solely using signatures of host range encoded in viral genomes. Within a dataset of 861 viral species with known zoonotic status, our approach outperformed models based on the phylogenetic relatedness of viruses to known human-infecting viruses (area under the receiver operating characteristic curve [AUC] = 0.773), distinguishing high-risk viruses within families that contain a minority of human-infecting species and identifying putatively undetected or so far unrealized zoonoses. Analyses of the underpinnings of model predictions suggested the existence of generalizable features of viral genomes that are independent of virus taxonomic relationships and that may preadapt viruses to infect humans. Our model reduced a second set of 645 animal-associated viruses that were excluded from training to 272 high and 41 very high-risk candidate zoonoses and showed significantly elevated predicted zoonotic risk in viruses from nonhuman primates, but not other mammalian or avian host groups. A second application showed that our models could have identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as a relatively high-risk coronavirus strain and that this prediction required no prior knowledge of zoonotic Severe Acute Respiratory Syndrome (SARS)-related coronaviruses. Genome-based zoonotic risk assessment provides a rapid, low-cost approach to enable evidence-driven virus surveillance and increases the feasibility of downstream biological and ecological characterization of viruses.

Innate and Adaptive Immune Genes Associated with MERS-CoV Infection in Dromedaries.

The recent SARS-CoV-2 pandemic has refocused attention to the betacoronaviruses, only eight years after the emergence of another zoonotic betacoronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV). While the wild source of SARS-CoV-2 may be disputed, for MERS-CoV, dromedaries are considered as source of zoonotic human infections. Testing 100 immune-response genes in 121 dromedaries from United Arab Emirates (UAE) for potential association with present MERS-CoV infection, we identified candidate genes with important functions in the adaptive, MHC-class I (HLA-A-24-like) and II (HLA-DPB1-like), and innate immune response (PTPN4, MAGOHB), and in cilia coating the respiratory tract (DNAH7). Some of these genes previously have been associated with viral replication in SARS-CoV-1/-2 in humans, others have an important role in the movement of bronchial cilia. These results suggest similar host genetic pathways associated with these betacoronaviruses, although further work is required to better understand the MERS-CoV disease dynamics in both dromedaries and humans.

Codon usage analysis of zoonotic coronaviruses reveals lower adaptation to humans by SARS-CoV-2.

Since 2002, the world has witnessed major outbreaks of acute respiratory illness by three zoonotic coronaviruses (CoVs), which differ from each other in pathogenicity. Reasons for the lower pathogenicity of SARS-CoV-2 than the other two zoonotic coronaviruses, SARS-CoV and MERS-CoV, are not well understood. We herein compared the codon usage patterns of the three zoonotic CoVs causing severe acute respiratory syndromes and four human-specific CoVs (NL63, 229E, OC43, and HKU1) causing mild diseases. We found that the seven viruses have different codon usages, with SARS-CoV-2 having the lowest effective number of codons (ENC) among the zoonotic CoVs. Human codon adaptation index (CAI) analysis revealed that the CAI value of SARS-CoV-2 is the lowest among the zoonotic CoVs. The ENC and CAI values of SARS-CoV-2 were more similar to those of the less-pathogenic human-specific CoVs. To further investigate adaptive evolution within SARS-CoV-2, we examined codon usage patterns in 3573 genomes of SARS-CoV-2 collected over the initial 4 months of the pandemic. We showed that the ENC values and the CAI values of SARS-CoV-2 were decreasing over the period. The low ENC and CAI values could be responsible for the lower pathogenicity of SARS-CoV-2. While mutational pressure appears to shape codon adaptation in the overall genomes of SARS-CoV-2 and other zoonotic CoVs, the E gene of SARS-CoV-2, which has the highest codon usage bias, appears to be under strong natural selection. Data from the study contribute to our understanding of the pathogenicity and evolution of SARS-CoV-2 in humans.

[Formation of population gene pools of zoonotic viruses, potentially threatening biosafety].

The possible formation of population gene pools of zoonotic viruses with a respiratory route of transmission and a possibility of a pandemic at different stages of biosphere evolution is analyzed. Forming of Poxviruses  (Entomopoxvirinae) gene pool could be the beginning of transformation from Plants to Arthropoda (Carbon - 375 million years ago) with further evolution connected with Rodentia (Pliocene - 75-70 million years ago) and further separation of genera (500-300 thousand years ago), and respiratory transmission (epidemics) between humans (10-2 thousand years BC). Smallpox comeback would be possible. Orthomyxoviruses relicts (genus Isavirus) were possibly connected with Ichthya (Silurian - 500-410 million years ago), and then close interaction with Aves (the Cretaceous, 125-110 million years ago) with the division of genera and respiratory transmission (epidemics) between humans (10-2 thousand BC). Next pandemic of influenza A could be catastrophic in terms of the number of victims and economic damage.Coronaviruses formed a gene pool by interaction with Amphibia (subfamily Letovirinae) and then with Chiroptera in Tertiary (110-75 million years ago) with transformation to Artiodactyla (Eocene - 70-60 million years ago), and only 10-2 thousand years BC acquired the ability to a respiratory transmission and became Alphaviruses, a seasonal infection of humans. A similar situation is possible in the near future with SARS-CoV-2. Pandemics associated with zoonoses even more serious than COVID-19 are likely. Constant monitoring of  populational gene pools of zoonotic viruses is necessary.

Asymptomatic SARS-CoV-2 infection: is it all about being refractile to innate immune sensing of viral spare-parts?-Clues from exotic animal reservoirs.

A vast proportion of coronavirus disease 2019 (COVID-19) individuals remain asymptomatic and can shed severe acute respiratory syndrome (SARS-CoV) type 2 virus to transmit the infection, which also explains the exponential increase in the number of COVID-19 cases globally. Furthermore, the rate of recovery from clinical COVID-19 in certain pockets of the globe is surprisingly high. Based on published reports and available literature, here, we speculated a few immunovirological mechanisms as to why a vast majority of individuals remain asymptomatic similar to exotic animal (bats and pangolins) reservoirs that remain refractile to disease development despite carrying a huge load of diverse insidious viral species, and whether such evolutionary advantage would unveil therapeutic strategies against COVID-19 infection in humans. Understanding the unique mechanisms that exotic animal species employ to achieve viral control, as well as inflammatory regulation, appears to hold key clues to the development of therapeutic versatility against COVID-19.

How the zoonotic origins of SARS-CoV-2 ensure its survival as a human disease.

In December 2019, a new species of coronavirus (SARS-CoV-2) was identified in a number of patients presenting with pneumonias of unknown aetiology in WuHan Province, China. Early epidemiological indications were of a zoonotic origin: many of the initial patients confirmed contact with a local wet market and the genomic sequencing showed similar characteristics with coronaviruses known to be carried by bats. The theory of subsequent human to human transmission became evident once global epidemiological reporting of COVID infection was established. Confirmation of the origins of infections caused by SARS-CoV-2 was enabled by the early sharing of the initial genomic sequence by China in January 2020 and since developed collaboratively on a globally accessible database, supported by the World Health Organization (https://tinyurl.com/rj32fp3).

The global spread of 2019-nCoV: a molecular evolutionary analysis.

The global spread of the 2019-nCoV is continuing and is fast moving, as indicated by the WHO raising the risk assessment to high. In this article, we provide a preliminary phylodynamic and phylogeographic analysis of this new virus. A Maximum Clade Credibility tree has been built using the 29 available whole genome sequences of 2019-nCoV and two whole genome sequences that are highly similar sequences from Bat SARS-like Coronavirus available in GeneBank. We are able to clarify the mechanism of transmission among the countries which have provided the 2019-nCoV sequence isolates from their patients. The Bayesian phylogeographic reconstruction shows that the 2019-2020 nCoV most probably originated from the Bat SARS-like Coronavirus circulating in the Rhinolophus bat family. In agreement with epidemiological observations, the most likely geographic origin of the new outbreak was the city of Wuhan, China, where 2019-nCoV time of the most recent common ancestor emerged, according to molecular clock analysis, around November 25th, 2019. These results, together with previously recorded epidemics, suggest a recurring pattern of periodical epizootic outbreaks due to Betacoronavirus. Moreover, our study describes the same population genetic dynamic underlying the SARS 2003 epidemic, and suggests the urgent need for the development of effective molecular surveillance strategies of Betacoronavirus among animals and Rhinolophus of the bat family.