Independent Epidemic Patterns of HIV-1 CRF01_AE Lineages Driven by Mobile Population in Shenzhen, an Immigrant city of China

Shenzhen, a city with > 12 million migrant population, may play a key role in the spread of HIV-1 in China. The transmission dynamics of CRF01_AE, a predominant subtype in Shenzhen, is a good model to characterize the impact of human mobility on HIV-1 epidemic locally and nationally. We used phylodynamic and phylogeographic methods to estimate the viral transmission dynamics and migration trajectory of variable lineages based on 1,423 CRF01_AE sequences in Shenzhen sampled between 2006 and 2015. Eleven lineages of CRF01_AE were detected in Shenzhen. Of those, four main lineages originated during the 1990s. The basic viral reproduction number (R0) of them ranged 1.96-3.92. The effective viral reproduction number (Re) of two lineages prevalent among heterosexuals/people who inject drugs had reduced < 1 at the end of sampling, and the main sources were the intra-provincial immigrants (72%) for one and local residents of Shenzhen (91%) for another. Within two lineages among MSM, Re had been above or close to 1 at the end of sampling, and the immigrants from Jiangxi/Shaanxi and Hubei as sources accounted for 93% and 68% of all viral migration events, respectively. Moreover, no obvious recipients were found throughout the viral migration history for any lineage. Our findings demonstrate that HIV declining epidemic in Shenzhen coincided with the initiation of the interventions during the 2000s. However, the obvious differences of the epidemic patterns between lineages emphasize the importance of further targeting interventions and continued molecular tracing, focusing on high-risk transmission sources among MSM.

Apoptosis Enhances the Replication of Human Coronavirus OC43

Human coronavirus OC43 (HCoV-OC43) is one of the coronaviruses causing a mild common cold, but few studies have been made on this strain. Here, we identified the molecular mechanisms involved in HCoV-OC43-induced apoptosis and its implications for viral reproduction in Vero cells and MRC-5 cells. HCoV-OC43 infection induced apoptosis that was accompanied by cleavage of caspase-3 and PARP, degradation of cyclin D1, and cell cycle arrest at S and G2M phases. Dephosphorylation of STAT1 and STAT3, induced by HCoV-OC43 infection, was also associated with HCoV-OC43-mediated apoptosis. The pan-caspase inhibitor effectively prevented HCoV-OC43-induced apoptosis and reduced viral replication, suggesting that apoptosis contributes to viral replication. Collectively our results indicate that HCoV-OC43 induces caspase-dependent apoptosis to promote viral replication in Vero cells and MRC-5 cells.

Discrete biological modeling for the immune response to dengue virus

Dengue infection affects more than half of the world’s population, with 1 billion symptomatic cases identified per year and several distinct genetic serotypes: DENV 1–4. Transmitted via the mosquito bite, the dengue virus infects Langerhans cells. Monocytes, B lymphocytes, and mast cells infected with dengue virus produce various cytokines although it is not clear which ones are predominant during DHF disease. A mathematical model of the Dengue virus infection is developed according to complex dynamics determined by many factors. Starting from a state of equilibrium that we could define as “virus-free” asymptotically stable with a viral reproduction number lower than one which means a very effective action of the innate immune system: it stops the infectious process, the mathematical analysis of stability in the presence of the virus demonstrates that the proposed model is dynamically influenced. Dengue fever affects more than half of the world’s population, with 1 billion symptomatic cases and multiple genetic serotypes confirmed each year, which simulates a network of interactions between the various populations involved without considering the speeds of the processes in question which are indicated in a separate computation. In this research, a hybrid approach of petri nets is utilized to connect the discrete models of dengue.

Possible future waves of SARS-CoV-2 infection generated by variants of concern with a range of characteristics

Viral reproduction of SARS-CoV-2 provides opportunities for the acquisition of advantageous mutations, altering viral transmissibility, disease severity, and/or allowing escape from natural or vaccine-derived immunity. We use three mathematical models: a parsimonious deterministic model with homogeneous mixing; an age-structured model; and a stochastic importation model to investigate the effect of potential variants of concern (VOCs). Calibrating to the situation in England in May 2021, we find epidemiological trajectories for putative VOCs are wide-ranging and dependent on their transmissibility, immune escape capability, and the introduction timing of a postulated VOC-targeted vaccine. We demonstrate that a VOC with a substantial transmission advantage over resident variants, or with immune escape properties, can generate a wave of infections and hospitalisations comparable to the winter 2020-2021 wave. Moreover, a variant that is less transmissible, but shows partial immune-escape could provoke a wave of infection that would not be revealed until control measures are further relaxed.

Discovery of Chalcone-Based Hybrid Structures as High Affinity and Site-Specific Inhibitors Against COVID-19; a Study Based on Various Host-Based and Viral Targets

3-Chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are at the forefront of attention for finding therapeutic agents for the treatment of COVID-19. In addition, proper modulation of host-based antiviral targets (HBATs) has also been highlighted by scientists as a promising approach for the suppression of the SARS-CoV-2. Previous studies indicated that some natural-based chalcones have significant inhibitory effect on the coronavirus enzymes 3CLpro and PLpro as well as modulation of some HBATs. In this study, a computational screening was performed to investigate the affinity of our compound library consisting of 757 chalcone-based structures (CHA-1 to CHA-757) for inhibiting the 3CLpro and PLpro enzymes, and also against twelve selected host-based targets. The twelve selected HBATs were chosen based on their involvement in viral reproduction. Our results indicated that CHA-12 (VUF 4819) is the most potent and a multi-target inhibitor in our chemical library over all viral and host-based targets. Correspondingly, CHA-384 and its congeners containing ureide moieties were found to be potent and selective 3CLpro inhibitors, and benzotriazole moiety in CHA-37 was found to be a main fragment for inhibiting the 3CLpro and PLpro. Surprisingly, our results were fully consistent with recent reports on the site-specific 3CLpro inhibitors. The results also indicate that the ureide and sulfonamide moieties are integral fragments for the optimum 3CLpro inhibition while occupying the S1 and S3 subsites. Finding the multi-target inhibitor CHA-12, previously reported as a LTD4 antagonist for the treatment of inflammatory pulmonary diseases, prompted us to suggest it as a concomitant antiviral agent for relieving respiratory symptoms and suppressing COVID-19 infection.

Antiviral Activity of Rosa damascena Mill. and Rosa alba L. Essential Oils against the Multiplication of Herpes Simplex Virus Type 1 Strains Sensitive and Resistant to Acyclovir

Background: The specific chemotherapeutics against herpes simplex virus type 1 (HSV) are nucleoside analogues such as acyclovir (ACV), but the most important problem is the formation of resistant mutants. The search for new therapeutic alternatives leads us to the purpose of investigating the effects of Rosa damascena Mill. and Rosa alba L. essential oils on the viral reproduction of susceptible (Victoria) and acyclovir-resistant (R-100) strains of HSV-1 replication in vitro, individually and in combination with acyclovir. Methods: Cytopathic effect inhibition test was used for assessment of antiviral activity of the oils, and the three-dimensional model of Prichard and Shipman was applied to evaluate the combined effect of oils with ACV on HSV-1 replication. Results: Both oils do not affect the replication of viral strains; they are able to influence only viral adsorption and extracellular virions and protect healthy cells from subsequent infection. In combination with lower doses of acyclovir, both oils demonstrate a significant synergistic effect on the replication of HSV-1, which is more contagious than the Victoria strain. Conclusions: The nonspecific mechanism of the reduction in viral reproduction caused by rose oils and the synergistic effect of their co-administration with the lower doses of specific inhibitor ACV makes them suitable therapeutics for overcoming viral resistance to HSV-1 infections.

Possible future waves of SARS-CoV-2 infection generated by variants of concern with a range of characteristics

Ongoing infection with, and associated viral reproduction of, SARS-CoV-2 provides opportunities for the virus to acquire advantageous mutations, which may alter viral transmissibility and disease severity, and allow escape from natural or vaccine-derived immunity. The number of countries reporting Variants of Concern (VOCs) with such mutations continues to rise. Here, we investigate two scenarios for third waves of the COVID pandemic: one driven by increased transmissibility, and another driven by immune escape. We do this using three mathematical models: a parsimonious susceptible-latent-infectious-recovered (SEIR) deterministic model with homogeneous mixing, an age-structured SARS-CoV-2 transmission model and a stochastic importation model. We calibrated our models to the situation in England in May 2021, although the insights will generalise to other contexts. We therefore accurately captured infection dynamics and vaccination rates, and also used these to explore the potential impact of a putative new VOC-targeted vaccine. Epidemiological trajectories for putative VOCs are wide-ranging and heavily dependent on their transmissibility, immune escape capability, and the time at which a postulated VOC-targeted vaccine may be introduced. We demonstrate that a VOC with either a substantial transmission advantage over resident variants, or the ability to evade vaccine-derived and prior immunity, is expected to generate a wave of infections and hospitalisations comparable to those seen in the winter 2020-21 wave. Moreover, a variant that is less transmissible, but shows partial immune-escape could provoke a wave of infection that would not be revealed until control measures are further relaxed.

Simultaneous fasting may contain SARS-CoV-2 infection

Fasting can halt viral reproduction and relieve symptoms. Simultaneous fasting with moderate intake of boiled rice water or fruit juice for 2 to 3 days may achieve positive effect. If a person has 30 contacts daily, and 6 of which are viral carriers, simultaneous fasting can reduce viral loads in all the 6 carriers and thus lower infection rate by perhaps more than 90%. Individuals not suitable for fasting should be excluded from pilot test and large experiments. Multiple episodes of fasting with proper intervals can be conducted to beat pandemic or control viral infection at its infancy.

Assessing the efficiency of COVID-19 NPIs in France: a retrospective study using a novel methodology

After an initial phase of low reactivity from the French public health authorities, in the face of the emergence of SARS-CoV-2 in February 2020, various Non Pharmaceutical Interventions (NPIs) were put in place (strict stay-at-home orders, followed by mandatory mask wearing in public places, curfews, partial lockdowns, etc.). In our knowledge, no study has independently assessed their respective effectiveness in an independent manner nor a synergistic manner. Our study has retrospectively studied (from 03/01/2020 to 30/01/2021), using metropolitan France data, the association strength (using normalized mutual information) as well as the linear correlation (using Pearson’s correlation) between more restrictive NPIs (mrNPIs) and epidemiological markers of COVID-19. All mrNPIs were moderately associated with a viral reproduction rate decrease but were associated neither with a decrease in COVID-19 daily hospitalizations, nor with COVID-19 daily ICU admissions. This paper is only for academic discussion, conclusions need to be confirmed by further research. Data and codes were available here http://gitlab.com/covid-data-2/lockdown-and-curfew.

Diversity of Plant Virus Movement Proteins: What Do They Have in Common?

The modern view of the mechanism of intercellular movement of viruses is based largely on data from the study of the tobacco mosaic virus (TMV) 30-kDa movement protein (MP). The discovered properties and abilities of TMV MP, namely, (a) in vitro binding of single-stranded RNA in a non-sequence-specific manner, (b) participation in the intracellular trafficking of genomic RNA to the plasmodesmata (Pd), and (c) localization in Pd and enhancement of Pd permeability, have been used as a reference in the search and analysis of candidate proteins from other plant viruses. Nevertheless, although almost four decades have passed since the introduction of the term “movement protein” into scientific circulation, the mechanism underlying its function remains unclear. It is unclear why, despite the absence of homology, different MPs are able to functionally replace each other in trans-complementation tests. Here, we consider the complexity and contradictions of the approaches for assessment of the ability of plant viral proteins to perform their movement function. We discuss different aspects of the participation of MP and MP/vRNA complexes in intra- and intercellular transport. In addition, we summarize the essential MP properties for their functioning as “conditioners”, creating a favorable environment for viral reproduction.