Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant

Background. The Omicron SARS-CoV-2 variant is responsible for a major wave of COVID-19, with record case counts reflecting high transmissibility and escape from prior immunity. Defining the time course of Omicron viral proliferation and clearance is crucial to inform isolation protocols aiming to minimize disease spread. Methods. We obtained longitudinal, quantitative RT-qPCR test results using combined anterior nares and oropharyngeal samples (n = 10,324) collected between July 5th, 2021 and January 10th, 2022 from the National Basketball Association's (NBA) occupational health program. We quantified the fraction of tests with PCR cycle threshold (Ct) values <30, chosen as a proxy for potential infectivity and antigen test positivity, on each day after first detection of suspected and confirmed Omicron infections, stratified by individuals detected under frequent testing protocols and those detected due to symptom onset or concern for contact with an infected individual. We quantified the duration of viral proliferation, clearance rate, and peak viral concentration for individuals with acute Omicron and Delta variant SARS-CoV-2 infections. Results. A total of 97 infections were confirmed or suspected to be from the Omicron variant and 107 from the Delta variant. Of 27 Omicron-infected individuals testing positive ≤1 day after a previous negative or inconclusive test, 52.0% (13/25) were PCR positive with Ct values <30 at day 5, 25.0% (6/24) at day 6, and 13.0% (3/23) on day 7 post detection. Of 70 Omicron-infected individuals detected ≥2 days after a previous negative or inconclusive test, 39.1% (25/64) were PCR positive with Ct values <30 at day 5, 33.3% (21/63) at day 6, and 22.2% (14/63) on day 7 post detection. Overall, Omicron infections featured a mean duration of 9.87 days (95% CI 8.83-10.9) relative to 10.9 days (95% CI 9.41-12.4) for Delta infections. The peak viral RNA based on Ct values was lower for Omicron infections than for Delta infections (Ct 23.3, 95% CI 22.4-24.3 for Omicron; Ct 20.5, 95% CI 19.2-21.8 for Delta) and the clearance phase was shorter for Omicron infections (5.35 days, 95% CI 4.78-6.00 for Omicron; 6.23 days, 95% CI 5.43-7.17 for Delta), though the rate of clearance was similar (3.13 Ct/day, 95% CI 2.75-3.54 for Omicron; 3.15 Ct/day, 95% CI 2.69-3.64 for Delta). Conclusions. While Omicron infections feature lower peak viral RNA and a shorter clearance phase than Delta infections on average, it is unclear to what extent these differences are attributable to more immunity in this largely vaccinated population or intrinsic characteristics of the Omicron variant. Further, these results suggest that Omicron's infectiousness may not be explained by higher viral load measured in the nose and mouth by RT-PCR. The substantial fraction of individuals with Ct values <30 at days 5 of infection, particularly in those detected due to symptom onset or concern for contact with an infected individual, underscores the heterogeneity of the infectious period, with implications for isolation policies.

Potent and Selective Covalent Inhibitors of the Papain-like Protease from SARS-CoV-2

Direct-acting antivirals for the treatment of COVID-19, which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), are needed to complement vaccination efforts. The papain-like protease (PLpro) of SARS-CoV-2 is essential for viral proliferation. In addition, PLpro dysregulates the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 protein (ISG15) from host proteins. As a result, PLpro is a promising target for inhibition by small-molecule therapeutics. Here we have designed a series of covalent inhibitors by introducing a peptidomimetic linker and reactive electrophilic “warheads” onto analogs of the noncovalent PLpro inhibitor GRL0617. We show that the most promising PLpro inhibitor is potent and selective, with activity in cell-based antiviral assays rivaling that of the RNA-dependent RNA polymerase inhibitor remdesivir. An X-ray crystal structure of the most promising lead compound bound covalently to PLpro establishes the molecular basis for protease inhibition and selectivity against structurally similar human deubiquitinases. These findings present an opportunity for further development of potent and selective covalent PLpro inhibitors.

Research Progress on the Structure and Function of G3BP

Ras-GTPase-activating protein (SH3 domain)-binding protein (G3BP) is an RNA binding protein. G3BP is a key component of stress granules (SGs) and can interact with many host proteins to regulate the expression of SGs. As an antiviral factor, G3BP can interact with viral proteins to regulate the assembly of SGs and thus exert antiviral effects. However, many viruses can also use G3BP as a proximal factor and recruit translation initiation factors to promote viral proliferation. G3BP regulates mRNA translation and attenuation to regulate gene expression; therefore, it is closely related to diseases, such as cancer, embryonic death, arteriosclerosis, and neurodevelopmental disorders. This review discusses the important discoveries and developments related G3BP in the biological field over the past 20 years, which includes the formation of SGs, interaction with viruses, stability of RNA, and disease progression.

Tissue-specific ramp sequences correspond with increased gene expression in humans and SARS-CoV-2

Translational ramp sequences are essential regulatory elements that have yet to be characterized in specific tissues. Ramp sequences increase gene expression by evenly spacing ribosomes and slowing initial translation. Therefore, the relative codon adaptiveness within different tissues changes the existence of a ramp sequence without altering the underlying genetic code. Here, we present the first comprehensive analysis of tissue and cell type-specific ramp sequences, and report 3,108 genes with ramp sequences that change between tissues and cell types. The Ramp Atlas (https://ramps.byu.edu/) is an accompanying web portal that allows researchers to query ramp sequences in 18,388 genes across 62 tissues and 66 cell types. We also identified seven SARS-CoV-2 genes and seven human SARS-CoV-2 entry factor genes with tissue-specific ramp sequences that may help explain viral proliferation within those tissues. We anticipate that The Ramp Atlas will facilitate future tissue-specific ramp sequence analyses to develop targeted therapeutics for human disease.

Mitochondrial Modulations, Autophagy Pathways Shifts in Viral Infections: Consequences of COVID-19

Mitochondria are vital intracellular organelles that play an important role in regulating various intracellular events such as metabolism, bioenergetics, cell death (apoptosis), and innate immune signaling. Mitochondrial fission, fusion, and membrane potential play a central role in maintaining mitochondrial dynamics and the overall shape of mitochondria. Viruses change the dynamics of the mitochondria by altering the mitochondrial processes/functions, such as autophagy, mitophagy, and enzymes involved in metabolism. In addition, viruses decrease the supply of energy to the mitochondria in the form of ATP, causing viruses to create cellular stress by generating ROS in mitochondria to instigate viral proliferation, a process which causes both intra- and extra-mitochondrial damage. SARS-COV2 propagates through altering or changing various pathways, such as autophagy, UPR stress, MPTP and NLRP3 inflammasome. Thus, these pathways act as potential targets for viruses to facilitate their proliferation. Autophagy plays an essential role in SARS-COV2-mediated COVID-19 and modulates autophagy by using various drugs that act on potential targets of the virus to inhibit and treat viral infection. Modulated autophagy inhibits coronavirus replication; thus, it becomes a promising target for anti-coronaviral therapy. This review gives immense knowledge about the infections, mitochondrial modulations, and therapeutic targets of viruses.

Viral dynamics of acute SARS-CoV-2 infection and applications to diagnostic and public health strategies

SARS-CoV-2 infections are characterized by viral proliferation and clearance phases and can be followed by low-level persistent viral RNA shedding. The dynamics of viral RNA concentration, particularly in the early stages of infection, can inform clinical measures and interventions such as test-based screening. We used prospective longitudinal quantitative reverse transcription PCR testing to measure the viral RNA trajectories for 68 individuals during the resumption of the 2019–2020 National Basketball Association season. For 46 individuals with acute infections, we inferred the peak viral concentration and the duration of the viral proliferation and clearance phases. According to our mathematical model, we found that viral RNA concentrations peaked an average of 3.3 days (95% credible interval [CI] 2.5, 4.2) after first possible detectability at a cycle threshold value of 22.3 (95% CI 20.5, 23.9). The viral clearance phase lasted longer for symptomatic individuals (10.9 days [95% CI 7.9, 14.4]) than for asymptomatic individuals (7.8 days [95% CI 6.1, 9.7]). A second test within 2 days after an initial positive PCR test substantially improves certainty about a patient’s infection stage. The effective sensitivity of a test intended to identify infectious individuals declines substantially with test turnaround time. These findings indicate that SARS-CoV-2 viral concentrations peak rapidly regardless of symptoms. Sequential tests can help reveal a patient’s progress through infection stages. Frequent, rapid-turnaround testing is needed to effectively screen individuals before they become infectious.

Pharmaceutical Prospects of Bee Products: Special Focus on Anticancer, Antibacterial, Antiviral, and Antiparasitic Properties

Bee products have long been used in traditional healing practices to treat many types of disorders, including cancer and microbial-related diseases. Indeed, several chemical compounds found in bee products have been demonstrated to display anticancer, antibacterial, antiviral, and antiparasitic properties. With the improvement of research tools and in view of recent advances related to bee products, this review aims to provide broad yet detailed insight into the pharmaceutical prospects of bee products such as honey, propolis, bee pollen, royal jelly, bee bread, beeswax, and bee venom, in the domain of cancer and infectious disease management. Available literature confirms the efficacy of these bee products in the alleviation of cancer progression, inhibition of bacterial and viral proliferation, and mitigation of parasitic-related symptoms. With such potentials, bioactive components isolated from the bee products can be used as an alternative approach in the long-run effort to improve humans’ health at a personal and community level.