Novel Proline derivatives for Treating COVID-19.

COVID-19 is a contagious disease. Paxlovid, a combination of Nirmatrelvir and Ritonavir, was granted emergency use authorization by the United States Food and Drug Administration (FDA) for the treatment of COVID-19 on December 22, 2021. These are peptidomimetic coronavirus main protease inhibitors. Nirmatrelvir is a proline derivative. The present patent describes similar proline- like compounds, their preparation, use, and pharmaceutical composition, and treatment.

Highly diverse ribonucleic acid viruses in the viromes of eukaryotic host species in Yunnan province, China.

Background: The diversity in currently documented viruses and their morphological characteristics indicates the need for understanding the evolutionary characteristics of viruses. Notably, further studies are needed to obtain a comprehensive landscape of virome, the virome of host species in Yunnan province, China. Materials and methods: We implemented the metagenomic next-generation sequencing strategy to investigate the viral diversity, which involved in 465 specimens collected from bats, pangolins, monkeys, and other species. The diverse RNA viruses were analyzed, especially focusing on the genome organization, genetic divergence and phylogenetic relationships. Results: In this study, we investigated the viral composition of eight libraries from bats, pangolins, monkeys, and other species, and found several diverse RNA viruses, including the Alphacoronavirus from bat specimens. By characterizing the genome organization, genetic divergence, and phylogenetic relationships, we identified five Alphacoronavirus strains, which shared phylogenetic association with Bat-CoV-HKU8-related strains. The pestivirus-like virus related to recently identified Dongyang pangolin virus (DYPV) strains from dead pangolin specimens, suggesting that these viruses are evolving. Some genomes showed higher divergence from known species (e.g., calicivirus CS9-Cali-YN-CHN-2020), and many showed evidence of recombination events with unknown or known strains (e.g., mamastroviruses BF2-astro-YN-CHN-2020 and EV-A122 AKM5-YN-CHN-2020). The newly identified viruses showed extensive changes and could be assigned as new species, or even genus (e.g., calicivirus CS9-Cali-YN-CHN-2020 and iflavirus Ifla-YN-CHN-2020). Moreover, we identified several highly divergent RNA viruses and estimated their evolutionary characteristics among different hosts, providing data for further examination of their evolutionary dynamics. Conclusion: Overall, our study emphasizes the close association between emerging viruses and infectious diseases, and the need for more comprehensive surveys.

Protein Nucleotidylylation in +ssRNA Viruses.

Nucleotidylylation is a post-transcriptional modification important for replication in the picornavirus supergroup of RNA viruses, including members of the Caliciviridae, Coronaviridae, Picornaviridae and Potyviridae virus families. This modification occurs when the RNA-dependent RNA polymerase (RdRp) attaches one or more nucleotides to a target protein through a nucleotidyl-transferase reaction. The most characterized nucleotidylylation target is VPg (viral protein genome-linked), a protein linked to the 5' end of the genome in Caliciviridae, Picornaviridae and Potyviridae. The nucleotidylylation of VPg by RdRp is a critical step for the VPg protein to act as a primer for genome replication and, in Caliciviridae and Potyviridae, for the initiation of translation. In contrast, Coronaviridae do not express a VPg protein, but the nucleotidylylation of proteins involved in replication initiation is critical for genome replication. Furthermore, the RdRp proteins of the viruses that perform nucleotidylylation are themselves nucleotidylylated, and in the case of coronavirus, this has been shown to be essential for viral replication. This review focuses on nucleotidylylation within the picornavirus supergroup of viruses, including the proteins that are modified, what is known about the nucleotidylylation process and the roles that these modifications have in the viral life cycle.

Screening of Eurasian Tundra Reindeer for Viral Sequences by Next-Generation Sequencing.

Reindeer husbandry is essential for the livelihood and culture of indigenous people in the Arctic. Parts of the herding areas are also used as pastures for farm animals, facilitating potential transmission of viruses between species. Following the Covid-19 pandemic, viruses circulating in the wild are receiving increased attention, since they might pose a potential threat to human health. Climate change will influence the prevalence of infectious diseases of both humans and animals. The aim of this study was to detect known and previously unknown viruses in Eurasian tundra reindeer. In total, 623 nasal and 477 rectal swab samples were collected from reindeer herds in Fennoscandia, Iceland, and Eastern Russia during 2016-2019. Next-generation sequencing analysis and BLAST-homology searches indicated the presence of viruses of domesticated and wild animals, such as bovine viral diarrhea virus, bovine papillomavirus, alcephaline herpesvirus 1 and 2, deer mastadenovirus B, bovine rotavirus, and roe deer picobirnavirus. Several viral species previously found in reindeer and some novel species were detected, although the clinical relevance of these viruses in reindeer is largely unknown. These results indicate that it should be possible to find emerging viruses of relevance for both human and animal health using reindeer as a sentinel species.

Non-influenza respiratory viruses in adult patients admitted with influenza-like illness: a 3-year prospective multicenter study.

PURPOSE: To describe the burden, and characteristics, of influenza-like illness (ILI) associated with non-influenza respiratory viruses (NIRV). METHODS: We performed a prospective, multicenter, observational study of adults admitted with ILI during three influenza seasons (2012-2015). Patients were screened for picornavirus, respiratory syncytial virus (RSV), coronavirus, human metapneumovirus, adenovirus, bocavirus, parainfluenza virus, and influenza, by PCR on nasopharyngeal samples. We excluded patients coinfected with NIRV and influenza. RESULTS: Among 1421 patients enrolled, influenza virus was detected in 535 (38%), and NIRV in 215 (15%), mostly picornavirus (n = 61), RSV (n = 53), coronavirus 229E (n = 48), and human metapneumovirus (n = 40). In-hospital mortality was 5% (NIRV), 4% (influenza), and 5% (no respiratory virus). As compared to influenza, NIRV were associated with age (median, 73 years vs. 68, P = 0.026), chronic respiratory diseases (53% vs. 45%, P = 0.034), cancer (14% vs. 9%, P = 0.029), and immunosuppressive drugs (21% vs. 14%, P = 0.028), and inversely associated with diabetes (18% vs. 25%, P = 0.038). On multivariable analysis, only chronic respiratory diseases (OR 1.5 [1.1-2.0], P = 0.008), and diabetes (OR 0.5 [0.4-0.8], P = 0.01) were associated with NIRV detection. CONCLUSIONS: NIRV are common in adults admitted with ILI during influenza seasons. Outcomes are similar in patients with NIRV, influenza, or no respiratory virus.

Conjunctivitis as a Sentinel of SARS-CoV-2 Infection: a Need of Revision for Mild Symptoms.

COVID-19 has been declared a pandemic by the World Health Organization on March 11, and since then, more than 3 million cases and a quarter million deaths have occurred due to it. Lately, there is a growing evidence for an ophthalmologic symptom (conjunctivitis) to be connected with the disease. This seems to happen in early stages of the infection by SARS-CoV-2, and thus, it is of major importance to understand the mechanism through which the virus can facilitate such a symptom. Here, we are proposing a molecular mechanism through which the novel coronavirus could act in order to affect the eye and use it as another, secondary but alternative, point of entry to the host organism.