SARS-CoV-2: lessons from both the history of medicine and from the biological behavior of other well-known viruses.

SARS-CoV-2 is the etiological agent of the current pandemic worldwide and its associated disease COVID-19. In this review, we have analyzed SARS-CoV-2 characteristics and those ones of other well-known RNA viruses viz. HIV, HCV and Influenza viruses, collecting their historical data, clinical manifestations and pathogenetic mechanisms. The aim of the work is obtaining useful insights and lessons for a better understanding of SARS-CoV-2. These pathogens present a distinct mode of transmission, as SARS-CoV-2 and Influenza viruses are airborne, whereas HIV and HCV are bloodborne. However, these viruses exhibit some potential similar clinical manifestations and pathogenetic mechanisms and their understanding may contribute to establishing preventive measures and new therapies against SARS-CoV-2.

Role of Host-Mediated Post-Translational Modifications (PTMs) in RNA Virus Pathogenesis.

Being opportunistic intracellular pathogens, viruses are dependent on the host for their replication. They hijack host cellular machinery for their replication and survival by targeting crucial cellular physiological pathways, including transcription, translation, immune pathways, and apoptosis. Immediately after translation, the host and viral proteins undergo a process called post-translational modification (PTM). PTMs of proteins involves the attachment of small proteins, carbohydrates/lipids, or chemical groups to the proteins and are crucial for the proteins' functioning. During viral infection, host proteins utilize PTMs to control the virus replication, using strategies like activating immune response pathways, inhibiting viral protein synthesis, and ultimately eliminating the virus from the host. PTM of viral proteins increases solubility, enhances antigenicity and virulence properties. However, RNA viruses are devoid of enzymes capable of introducing PTMs to their proteins. Hence, they utilize the host PTM machinery to promote their survival. Proteins from viruses belonging to the family: Togaviridae, Flaviviridae, Retroviridae, and Coronaviridae such as chikungunya, dengue, zika, HIV, and coronavirus are a few that are well-known to be modified. This review discusses various host and virus-mediated PTMs that play a role in the outcome during the infection.

The role of A-to-I RNA editing in infections by RNA viruses: Possible implications for SARS-CoV-2 infection.

RNA editing is a fundamental biological process with 2 major forms, namely adenosine-to-inosine (A-to-I, recognized as A-to-G) and cytosine-to-uracil (C-to-U) deamination, mediated by ADAR and APOBEC enzyme families, respectively. A-to-I RNA editing has been shown to directly affect the genome/transcriptome of RNA viruses with significant repercussions for viral protein synthesis, proliferation and infectivity, while it also affects recognition of double-stranded RNAs by cytosolic receptors controlling the host innate immune response. Recent evidence suggests that RNA editing may be present in SARS-CoV-2 genome/transcriptome. The majority of mapped mutations in SARS-CoV-2 genome are A-to-G/U-to-C(opposite strand) and C-to-U/G-to-A(opposite strand) substitutions comprising potential ADAR-/APOBEC-mediated deamination events. A single nucleotide substitution can have dramatic effects on SARS-CoV-2 infectivity as shown by the D614G(A-to-G) substitution in the spike protein. Future studies utilizing serial sampling from patients with COVID-19 are warranted to delineate whether RNA editing affects viral replication and/or the host immune response to SARS-CoV-2.

Ocular manifestations of emerging viral diseases.

Emerging infectious diseases (EIDs) are an increasing threat to public health on a global scale. In recent times, the most prominent outbreaks have constituted RNA viruses, spreading via droplets (COVID-19 and Influenza A H1N1), directly between humans (Ebola and Marburg), via arthropod vectors (Dengue, Zika, West Nile, Chikungunya, Crimean Congo) and zoonotically (Lassa fever, Nipah, Rift Valley fever, Hantaviruses). However, specific approved antiviral therapies and vaccine availability are scarce, and public health measures remain critical. Patients can present with a spectrum of ocular manifestations. Emerging infectious diseases should therefore be considered in the differential diagnosis of ocular inflammatory conditions in patients inhabiting or returning from endemic territories, and more general vigilance is advisable in the context of a global pandemic. Eye specialists are in a position to facilitate swift diagnosis, improve clinical outcomes, and contribute to wider public health efforts during outbreaks. This article reviews those emerging viral diseases associated with reports of ocular manifestations and summarizes details pertinent to practicing eye specialists.

mTOR inhibition in COVID-19: A commentary and review of efficacy in RNA viruses.

In this commentary, we shed light on the role of the mammalian target of rapamycin (mTOR) pathway in viral infections. The mTOR pathway has been demonstrated to be modulated in numerous RNA viruses. Frequently, inhibiting mTOR results in suppression of virus growth and replication. Recent evidence points towards modulation of mTOR in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We discuss the current literature on mTOR in SARS-CoV-2 and highlight evidence in support of a role for mTOR inhibitors in the treatment of coronavirus disease 2019.

The International Virus Bioinformatics Meeting 2020.

The International Virus Bioinformatics Meeting 2020 was originally planned to take place in Bern, Switzerland, in March 2020. However, the COVID-19 pandemic put a spoke in the wheel of almost all conferences to be held in 2020. After moving the conference to 8-9 October 2020, we got hit by the second wave and finally decided at short notice to go fully online. On the other hand, the pandemic has made us even more aware of the importance of accelerating research in viral bioinformatics. Advances in bioinformatics have led to improved approaches to investigate viral infections and outbreaks. The International Virus Bioinformatics Meeting 2020 has attracted approximately 120 experts in virology and bioinformatics from all over the world to join the two-day virtual meeting. Despite concerns being raised that virtual meetings lack possibilities for face-to-face discussion, the participants from this small community created a highly interactive scientific environment, engaging in lively and inspiring discussions and suggesting new research directions and questions. The meeting featured five invited and twelve contributed talks, on the four main topics: (1) proteome and RNAome of RNA viruses, (2) viral metagenomics and ecology, (3) virus evolution and classification and (4) viral infections and immunology. Further, the meeting featured 20 oral poster presentations, all of which focused on specific areas of virus bioinformatics. This report summarizes the main research findings and highlights presented at the meeting.

Potential neuroinvasive and neurotrophic properties of SARS-CoV-2 in pediatric patients: comparison of SARS-CoV-2 with non-segmented RNA viruses.

The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing global health crises. Children can be infected, but are less likely to develop severe neurological abnormalities compared with adults. However, whether SARS-CoV-2 can directly cause neurological impairments in pediatric patients is not known. The possible evolutionary and molecular relationship between SARS-CoV-2 and non-segmented RNA viruses were examined with reference to neurological disorders in pediatric patients. SARS-CoV-2 shares similar functional domains with neuroinvasive and neurotropic RNA viruses. The Spike 1 (S1) receptor binding domain and the cleavage sites at S1/S2 boundary are less conserved compared with the S2 among coronaviruses.