Azolopyrimidine-Based Thioethers: Synthesis via Cross-Dehydrogenative C-S Coupling and In Silico Evaluation of Anti-SARS-CoV-2 Activity.

Azoloazine derivatives are known as promising small molecules that are potentially able to counteract a broad spectrum of RNA viruses including SARS-CoV-2. However, a pool of synthetic pathways to provide convenient structural modification of such compounds without de novo construction of the heterocyclic scaffold is rather limited so far. This work proposes an approach to the direct C(sp)-H functionalization of azolopyrimidine substrates with aromatic thiol residues, mediated by the iodine/persulfate reagent system.

Immunogenicity and Protective Efficacy of a Single Intranasal Dose Vectored Vaccine Based on Sendai Virus (Moscow Strain) against SARS-CoV-2 Variant of Concern.

The mouse paramyxovirus Sendai, which is capable of limited replication in human bronchial epithelial cells without causing disease, is well suited for the development of vector-based intranasal vaccines against respiratory infections, including SARS-CoV-2. Using the Moscow strain of the Sendai virus, we developed a vaccine construct, Sen-Sdelta(M), which expresses the full-length spike (S) protein of the SARS-CoV-2 delta variant. A single intranasal delivery of Sen-Sdelta(M) to Syrian hamsters and BALB/c mice induced high titers of virus-neutralizing antibodies specific to the SARS-CoV-2 delta variant.

Influence of Viscosity on Variously Scaled Batch Cooling Crystallization from Aqueous Erythritol, Glucose, Xylitol, and Xylose Solutions.

This study presents a comprehensive comparison of the batch cooling crystallization performance of aqueous solutions containing sugars and sugar alcohols, namely, erythritol, glucose, xylitol, and xylose. Erythritol and xylitol are commonly used alternative sweeteners to replace sucrose. They can be obtained by fermentation-based bioprocesses, where glucose and xylose are typical raw materials.

Pre-Pandemic Cross-Reactive Immunity against SARS-CoV-2 among Siberian Populations.

In December 2019, a new coronavirus, SARS-CoV-2, was found to in Wuhan, China. Cases of infection were subsequently detected in other countries in a short period of time, resulting in the declaration of the COVID-19 pandemic by the World Health Organization (WHO) on 11 March 2020. Questions about the impact of herd immunity of pre-existing immune reactivity to SARS-CoV-2 on COVID-19 severity, associated with the immunity to seasonal manifestation, are still to be resolved and may be useful for understanding some processes that precede the emergence of a pandemic virus.

Gamma-valerolactone biorefinery: Catalyzed birch fractionation and valorization of pulping streams with solvent recovery.

In this study, we propose a full gamma-valerolactone (GVL) organosolv biorefinery concept including the utilization of all pulping streams, solvent recovery, and preliminary material and energy balances. GVL is a renewable and non-toxic solvent that fractionates woody biomass. The silver birch chips were pulped (45-65 wt% GVL, 150 °C, 2 h) under a series of acid-catalyzed conditions (5-12 kg HSO/t), and the fully bleached pulp was spun into fibers by the IONCELL® process and knitted into the fabric.

SARS-CoV-2 RBD Conjugated to Polyglucin, Spermidine, and dsRNA Elicits a Strong Immune Response in Mice.

Despite the rapid development and approval of several COVID vaccines based on the full-length spike protein, there is a need for safe, potent, and high-volume vaccines. Considering the predominance of the production of neutralizing antibodies targeting the receptor-binding domain (RBD) of S-protein after natural infection or vaccination, it makes sense to choose RBD as a vaccine immunogen. However, due to its small size, RBD exhibits relatively poor immunogenicity.

Batch Crystallization of Xylitol by Cooling, Evaporative, and Antisolvent Crystallization.

Four different techniques for xylitol crystallization, namely cooling, evaporative, antisolvent, and combined antisolvent and cooling crystallization, were investigated regarding their influence on the product crystal properties. Various batch times and mixing intensities were studied, and the antisolvent used was ethanol. Real-time monitoring of the count rates of various chord length fractions and distributions using focused beam reflectance measurement was conducted.

Optimization of In Vivo Electroporation Conditions and Delivery of DNA Vaccine Encoding SARS-CoV-2 RBD Using the Determined Protocol.

Vaccination against SARS-CoV-2 and other viral infections requires safe, effective, and inexpensive vaccines that can be rapidly developed. DNA vaccines are candidates that meet these criteria, but one of their drawbacks is their relatively weak immunogenicity. Electroporation (EP) is an effective way to enhance the immunogenicity of DNA vaccines, but because of the different configurations of the devices that are used for EP, it is necessary to carefully select the conditions of the procedure, including characteristics such as voltage, current strength, number of pulses, etc.

Borneol Ester Derivatives as Entry Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses.

In the present work we studied the antiviral activity of the home library of monoterpenoid derivatives using the pseudoviral systems of our development, which have glycoproteins of the SARS-CoV-2 virus strains Wuhan and Delta on their surface. We found that borneol derivatives with a tertiary nitrogen atom can exhibit activity at the early stages of viral replication. In order to search for potential binding sites of ligands with glycoprotein, we carried out additional biological tests to study the inhibition of the re-receptor-binding domain of protein S.

Are Hamsters a Suitable Model for Evaluating the Immunogenicity of RBD-Based Anti-COVID-19 Subunit Vaccines?

Currently, SARS-CoV-2 spike receptor-binding-domain (RBD)-based vaccines are considered one of the most effective weapons against COVID-19. During the first step of assessing vaccine immunogenicity, a mouse model is often used. In this paper, we tested the use of five experimental animals (mice, hamsters, rabbits, ferrets, and chickens) for RBD immunogenicity assessments.

Self-Assembled Particles Combining SARS-CoV-2 RBD Protein and RBD DNA Vaccine Induce Synergistic Enhancement of the Humoral Response in Mice.

Despite the fact that a range of vaccines against COVID-19 have already been created and are used for mass vaccination, the development of effective, safe, technological, and affordable vaccines continues. We have designed a vaccine that combines the recombinant protein and DNA vaccine approaches in a self-assembled particle. The receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 was conjugated to polyglucin:spermidine and mixed with DNA vaccine (pVAXrbd), which led to the formation of particles of combined coronavirus vaccine (CCV-RBD) that contain the DNA vaccine inside and RBD protein on the surface.

Comparative Immunogenicity of the Recombinant Receptor-Binding Domain of Protein S SARS-CoV-2 Obtained in Prokaryotic and Mammalian Expression Systems.

The receptor-binding domain (RBD) of the protein S SARS-CoV-2 is considered to be one of the appealing targets for developing a vaccine against COVID-19. The choice of an expression system is essential when developing subunit vaccines, as it ensures the effective synthesis of the correctly folded target protein, and maintains its antigenic and immunogenic properties. Here, we describe the production of a recombinant RBD protein using prokaryotic (pRBD) and mammalian (mRBD) expression systems, and compare the immunogenicity of prokaryotic and mammalian-expressed RBD using a BALB/c mice model.

Synthesis and In Vitro Study of Antiviral Activity of Glycyrrhizin Nicotinate Derivatives against HIV-1 Pseudoviruses and SARS-CoV-2 Viruses.

When developing drugs against SARS-CoV-2, it is important to consider the characteristics of patients with different co-morbidities. People infected with HIV-1 are a particularly vulnerable group, as they may be at a higher risk than the general population of contracting COVID-19 with clinical complications. For such patients, drugs with a broad spectrum of antiviral activity are of paramount importance.

Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses.

To date, the 'one bug-one drug' approach to antiviral drug development cannot effectively respond to the constant threat posed by an increasing diversity of viruses causing outbreaks of viral infections that turn out to be pathogenic for humans. Evidently, there is an urgent need for new strategies to develop efficient antiviral agents with broad-spectrum activities. In this paper, we identified camphene derivatives that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses, including influenza virus A/PR/8/34 (H1N1), Ebola virus (EBOV), and the Hantaan virus.

Biostability study, quantitation method and preliminary pharmacokinetics of a new antifilovirus agent based on borneol and 3-(piperidin-1-yl)propanoic acid.

The stability of the new antifiloviral agent AS-358, which is a derivative of borneol and 3-(piperidin-1-yl)propanoic acid, was studied in the blood and blood plasma of rats in vitro. It was found that both in the blood and in the plasma stabilized by EDTA or heparin, the compound is rapidly hydrolyzed at the ester bond. When sodium fluoride was added to the whole blood, the decomposition of the compound was significantly slowed down, which made it possible to develop and validate a method for the quantitative determination of the agent in this matrix.

New class of hantaan virus inhibitors based on conjugation of the isoindole fragment to (+)-camphor or (-)-fenchone hydrazonesv.

This work presents the design and synthesis of camphor, fenchone, and norcamphor N-acylhydrazone derivatives as a new class of inhibitors of the Hantaan virus, which causes haemorrhagic fever with renal syndrome (HFRS). A cytopathic model was developed for testing chemotherapeutics against the Hantaan virus, strain 76-118. In addition, a study of the antiviral activity was carried out using a pseudoviral system.

Delivery of mRNA Vaccine against SARS-CoV-2 Using a Polyglucin:Spermidine Conjugate.

One of the key stages in the development of mRNA vaccines is their delivery. Along with liposome, other materials are being developed for mRNA delivery that can ensure both the safety and effectiveness of the vaccine, and also facilitate its storage and transportation. In this study, we investigated the polyglucin:spermidine conjugate as a carrier of an mRNA-RBD vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein.

Monoterpenoid-based inhibitors of filoviruses targeting the glycoprotein-mediated entry process.

In this study, we screened a large library of (+)-camphor and (-)-borneol derivatives to assess their filovirus entry inhibition activities using pseudotype systems. Structure-activity relationship studies revealed several compounds exhibiting submicromolar IC values. These compounds were evaluated for their effect against natural Ebola virus (EBOV) and Marburg virus.

Genetic and biological characterization of avian influenza H5N1 viruses isolated from wild birds and poultry in Western Siberia.

Three viruses included in the study were isolated from dead birds (A/duck/Omsk/1822/2006, A/chicken/Reshoty/02/2006, and A/duck/Tuva/01/2006), whereas the virus A/common gull/Chany/P/2006 was isolated from an apparently healthy gull during outbreaks of highly pathogenic avian influenza in Russia in 2006. The intravenous pathogenicity index (IVPI) of viruses A/duck/Omsk/1822/2006, A/chicken/Reshoty/02/2006, and A/duck/Tuva/01/2006 ranged from 2.7 to 3.

Experimental infection of H5N1 HPAI in BALB/c mice.

Background: In 2005 huge epizooty of H5N1 HPAI occurred in Russia. It had been clear that territory of Russia becoming endemic for H5N1 HPAI. In 2006 several outbreaks have occurred.

Influenza (H5N1) viruses in poultry, Russian Federation, 2005-2006.

We studied 7 influenza (H5N1) viruses isolated from poultry in western Siberia and the European part of the Russian Federation during July 2005-February 2006. Full genome sequences showed high homology to Qinghai-like influenza (H5N1) viruses. Phylogenetic analysis not only showed a close genetic relationship between the H5N1 strains isolated from poultry and wild migratory waterfowls but also suggested genetic reassortment among the analyzed isolates.