Identification of novel mammalian viruses in tree shrews ( Tupaia belangeri chinensis).

The Chinese tree shrew ( Tupaia belangeri chinensis), a member of the mammalian order Scandentia, exhibits considerable similarities with primates, including humans, in aspects of its nervous, immune, and metabolic systems. These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer, infectious diseases, metabolic disorders, and mental health conditions. Herein, we used meta-transcriptomic sequencing to analyze plasma, as well as oral and anal swab samples, from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses. In total, eight mammalian viruses with complete genomes were identified, belonging to six viral families, including Flaviviridae, Hepeviridae, Parvovirinae, Picornaviridae, Sedoreoviridae, and Spinareoviridae. Notably, the presence of rotavirus was recorded in tree shrews for the first time. Three viruses - hepacivirus 1, parvovirus, and picornavirus - exhibited low genetic similarity (<70%) with previously reported viruses at the whole-genome scale, indicating novelty. Conversely, three other viruses - hepacivirus 2, hepatovirus A and hepevirus - exhibited high similarity (>94%) to known viral strains. Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants. These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews, highlighting the necessity for further research into their potential for cross-species transmission.

Entangling of Peptide Nanofibers Reduces the Invasiveness of SARS-CoV-2.

The viral spike (S) protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells, facilitating its entry and infection. Here, functionalized nanofibers targeting the S protein with peptide sequences of IRQFFKK, WVHFYHK and NSGGSVH, which are screened from a high-throughput one-bead one-compound screening strategy, are designed and prepared. The flexible nanofibers support multiple binding sites and efficiently entangle SARS-CoV-2, forming a nanofibrous network that blocks the interaction between the S protein of SARS-CoV-2 and the ACE2 on host cells, and efficiently reduce the invasiveness of SARS-CoV-2. In summary, nanofibers entangling represents a smart nanomedicine for the prevention of SARS-CoV-2.

Synthesis and anti-HIV activity of non-nucleoside reverse-transcriptase inhibitor DB02 phosphate derivatives based on water-soluble optimization.

To improve the water solubility of anti-human immunodeficiency virus (HIV) agent DB02, an excellent non-nucleoside reverse-transcriptase inhibitor (NNRTI) obtained in our previous efforts, we designed and synthesized four phosphate derivatives of DB02 based on the molecular model of DB02 with RT. Here, the antiviral activity of these four derivatives was detected, leading to the discovery of compound P-2, which possessed a superior potency to the lead compound DB02 against wild-type HIV-1 and a variety of HIV-resistant mutant viruses significantly. Furthermore, the water solubility of P-2 was nearly 17 times higher than that of DB02, and the pharmacokinetic test in rats showed that P-2 demonstrate significantly improved oral bioavailablity of 14.6%. Our study showed that the introduction of a phosphate ester group at the end of the C-2 side chain of DB02 was beneficial to the improvement of its antiviral activity and pharmacokinetic properties, which provided a promising lead for the further development of S-DACOs type of NNRTIs.

A pair of new oxindole alkaloids isolated from Uncaria macrophylla.

A pair of new oxindole alkaloids, named macrophyllines C (1) and D (2), together with two known oxindole alkaloids isorhynchophylline (3) and corynoxine (4) were isolated from Uncaria macrophylla. Their structures were elucidated based on detailed spectroscopic analysis and by comparison with literature data. In addition, all the isolates were tested for their anti-HIV activities and cytotoxicities in C8166 cells and compounds 2-4 showed weak anti-HIV activities with EC50 values of 11.31 ± 3.29 µM, 18.77 ± 6.14 µM and 30.02 ± 3.73 µM, respectively.

A SIRD epidemic model with community structure.

The study of epidemics spreading with community structure has become a hot topic. The classic SIR epidemic model does not distinguish between dead and recovered individuals. It is inappropriate to classify dead individuals as recovered individuals because the real-world epidemic spread processes show different recovery rates and death rates in different communities. In the present work, a SIRD epidemic model with different recovery rates is proposed. We pay more attention to the changes in the number of dead individuals. The basic reproductive number is obtained. The stationary solutions of a disease-free state and an endemic state are given. We show that quarantining communities can decrease the basic reproductive number, and the total number of dead individuals decreases in a disease-free steady state with an increase in the number of quarantined communities. The most effective quarantining strategy is to preferentially quarantine some communities/cities with a greater population size and a fraction of initially infected individuals. Furthermore, we show that the population flows from a low recovery rate and high population density community/city/country to some high recovery rate and low population density communities/cities/countries, which helps to reduce the total number of dead individuals and prevent the prevalence of epidemics. The numerical simulations on the real-world network and the synthetic network further support our conclusions.

pH-sensitive chitosan nanoparticles loaded with dolutegravir as milk and food admixture for paediatric anti-HIV therapy.

The present study aims to develop Chitosan-based polymeric nanoparticles of anti-HIV drug Dolutegravir, to aid appropriate dose adjustment and ease of oral administration as milk and food admixture for children. The isolated Chitosan from the crab shell species Portunus Sanguinolentus has been characterized for their physicochemical properties. Nanoparticles were developed with varying ratio of drug: Chitosan and assessed for particle size (140-548 nm), zeta potential (+26.1 mV) with a maximum of 75 % drug content. Nanoparticles exhibited improved stability and drug release in the 0.1 N HCl medium compared to pure drug. The MTT assay and the Syncytia inhibition assay in C8166 (T-lymphatic cell line) infected with HIVIIIB viral strain, which showed better therapeutic efficiency and lesser cytotoxicity compared to the pure drug. In consonance with the data obtained, the use of chitosan from a novel source for drug delivery carrier has opened exceptional prospects for delivering drugs efficiently to paediatrics.

Epidemic spreading on multilayer homogeneous evolving networks.

Multilayer networks are widely used to characterize the dynamic behavior of complex systems. The study of epidemic spreading dynamics on multilayer networks has become a hot topic in network science. Although many models have been proposed to explore epidemic spreading across different networks, there is still a lack of models to study the spreading of diseases in the process of evolution on multilayer homogeneous networks. In the present work, we propose an epidemic spreading dynamic model of homogeneous evolving networks that can be used to analyze and simulate the spreading of epidemics on such networks. We determine the global epidemic threshold. We make the interesting discovery that increasing the epidemic threshold of a single network layer is conducive to mitigating the spreading of an epidemic. We find that the initial average degree of a network and the evolutionary parameters determine the changes in the epidemic threshold and the spreading process. An approach for calculating the falling and rising threshold zones is presented. Our work provides a good strategy to control epidemic spreading. Generally, controlling or changing the threshold in a single network layer is easier than trying to directly change the threshold in all network layers. Numerical simulations of small-world and random networks further support and enrich our conclusions.