Leucoverdazyls as Novel Potent Inhibitors of Enterovirus Replication.

Enteroviruses (EV) are important pathogens causing human disease with various clinical manifestations. To date, treatment of enteroviral infections is mainly supportive since no vaccination or antiviral drugs are approved for their prevention or treatment. Here, we describe the antiviral properties and mechanisms of action of leucoverdazyls-novel heterocyclic compounds with antioxidant potential. The lead compound, 1a, demonstrated low cytotoxicity along with high antioxidant and virus-inhibiting activity. A viral strain resistant to 1a was selected, and the development of resistance was shown to be accompanied by mutation of virus-specific non-structural protein 2C. This resistant virus had lower fitness when grown in cell culture. Taken together, our results demonstrate high antiviral potential of leucoverdazyls as novel inhibitors of enterovirus replication and support previous evidence of an important role of 2C proteins in EV replication.

Enterovirus 71-Associated Infection in South Vietnam: Vaccination Is a Real Solution.

Hand-foot-and-mouth disease (HFMD) is the most common enteroviral infection in South-East Asia. When evaluating the role of enterovirus 71 (EVA71) as an etiological agent of infectious disease in South Vietnam, we revealed a high proportion of EVA71 among identified species A enteroviruses found in 3542 samples from HFMD cases; 125 samples from cases of enteroviral meningitis; and 130 samples from acute flaccid paralysis (AFP) cases. These represent 50%, 54.8%, and 51.5%, respectively. According to molecular analysis, 90% of EVA71 were attributed to genotype C4 and 10% were attributed to genotype B5. The predominance of EVA71 circulation among the population proves the need to strengthen surveillance (with monitoring of enterovirus circulation for facilitation of HFMD outbreak prediction) and to increase the effectiveness of preventative measures by the implementation of vaccination against EVA71-associated infections. A phase III trial of a Taiwanese vaccine (EV71vac) in Taiwan and South Vietnam showed its safety, tolerability, and efficacy in children aged 2-71 months. This B4 genotype-based vaccine, which features cross-protection against B5 and C4 genotypes, and other existing EV71 vaccines can serve as a good approach to solving the HFMD problem, which is so important for Vietnam.

Correction: Gladkikh et al. Epidemiological Features of COVID-19 in Northwest Russia in 2021. Viruses 2022, 14, 931.

There was an error in the original publication [...].

Epidemiological Features of COVID-19 in Northwest Russia in 2021.

Appearing in Wuhan (China) and quickly spreading across the globe, the novel coronavirus infection quickly became a significant threat to global health. The year 2021 was characterized by both increases and decreases in COVID-19 incidence, and Russia was no exception. In this work, we describe regional features in the Northwestern federal district (FD) of Russia of the pandemic in 2021 based on Rospotrebnadzor statistics and data from SARS-CoV-2 genetic monitoring provided by the Saint Petersburg Pasteur Institute as a part of epidemiological surveillance. The epidemiological situation in the studied region was complicated by the presence of the megacity Saint Petersburg, featuring a high population density and its status as an international transport hub. COVID-19 incidence in the Northwestern FD fluctuated throughout the year, with two characteristic maxima in January and November. An analysis of fluctuations in the age structure, severity of morbidity, mortality rates, and the level of population vaccination in the region during the year is given. Assessment of epidemiological indicators was carried out in relation to changes in locally circulating genetic variants. It was seen that, during 2021, so-called variants of concern (VOC) circulated in the region (Alpha, Beta, Delta, Omicron), with Delta variant strains dominating from June to December. They successively replaced the variants of lines 20A and 20B circulating at the beginning of the year. An epidemiological feature of the northwestern region is the AT.1 variant, which was identified for the first time and later spread throughout the region and beyond its borders. Its share of the regional viral population reached 28.2% in May, and sporadic cases were observed until September. It has been shown that genetic variants of AT.1 lineages distributed in Russia and Northern Europe represent a single phylogenetic group at the base of the 20B branch on the global phylogenetic tree of SARS-CoV-2 strains. The progression of the COVID-19 pandemic occurred against the background of a vaccination campaign. The findings highlight the impact of vaccination on lowering severe COVID-19 case numbers and the mortality rate, despite ongoing changes in circulating SARS-CoV-2 genetic variants.

Characterization of a Novel SARS-CoV-2 Genetic Variant with Distinct Spike Protein Mutations.

The COVID-19 pandemic, which began in Wuhan (Hubei, China), has been ongoing for about a year and a half. An unprecedented number of people around the world have been infected with SARS-CoV-2, the etiological agent of COVID-19. Despite the fact that the mortality rate for COVID-19 is relatively low, the total number of deaths has currently already reached more than three million and continues to increase due to high incidence. Since the beginning of the pandemic, a large number of sequences have been obtained and many genetic variants have been identified. Some of them bear significant mutations that affect biological properties of the virus. These genetic variants, currently Variants of Concern (VoC), include the so-called United Kingdom variant (20I/501Y), the Brazilian variant (20J/501Y.V3), and the South African variant (20H/501Y.V2). We describe here a novel SARS-CoV-2 variant with distinct spike protein mutations, first obtained at the end of January 2021 in northwest Russia. Therefore, it is necessary to pay attention to the dynamics of its spread among patients with COVID-19, as well as to study in detail its biological properties.