Background: The effects of molnupiravir in treating COVID-19 remain uncertain. This systematic review aimed to evaluate the efficacy and safety of molnupiravir for adult patients with mild or moderate COVID-19.Methods: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the World Health Organization (WHO) COVID-19 database for randomised controlled trials (RCTs) up to December 27, 2022, comparing molnupiravir against standard care or placebo for treatment of adult patients with mild to moderate COVID-19. Paired reviewers independently identified studies and performed data extraction and risk of bias assessment. We performed DerSimonian-Laird random effects meta-analyses to summarize the evidence and evaluated the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. We registered the protocol with PROSPERO, CRD42023388517.Findings: Nine RCTs enrolling 30472 patients proved eligible. In adult patients with mild or moderate COVID-19, molnupiravir reduces mortality (relative risks (RR) 0.43, 95% CI 0.20 to 0.94, risk difference (RD) 0.7% fewer; high certainty), probably reduces the risk of hospital admission (RR 0.67, 95% CI 0.45 to 0.99, RD 1.8% fewer; moderate certainty), and may reduce time to viral clearance (MD -1.81 days, 95% CI -3.31 to -0.31; low certainty) and time to symptom resolution or clinical improvement (MD -2.39 days, 95% CI -3.71 to -1.07; low certainty). Molnupiravir probably increases rate of viral clearance (RR 3.47, 95% CI 2.43 to 4.96, RD 16.1% more; moderate certainty) at 7 days (± 3 days) and likely does not increase serious adverse events (RR 0.84, 95% CI 0.61 to 1.15, RD 0.1% fewer; moderate certainty).Interpretation: In adult patients with mild or moderate COVID-19, molnupiravir reduces mortality and likely reduces risk of hospital admission probably without increasing serious adverse events.Funding: None.Declaration of Interests: We declare no competing interests.
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has had a significant impact on healthcare systems and economies worldwide. The continuous emergence of new viral strains presents a major challenge in the development of effective antiviral agents. Strategies that possess broad-spectrum antiviral activities are desirable to control SARS-CoV-2 infection. ACE2, an angiotensin-containing enzyme that prevents the overactivation of the renin angiotensin system, is the receptor for SARS-CoV-2. ACE2 interacts with the spike protein and facilitates viral attachment and entry into host cells. Yet, SARS-CoV-2 infection also promotes ACE2 degradation. Whether restoring ACE2 surface expression has an impact on SARS-CoV-2 infection is yet to be determined. Here, we show that the ACE2-spike complex is endocytosed and degraded via autophagy in a manner that depends on clathrin-mediated endocytosis and PAK1-mediated cytoskeleton rearrangement. In contrast, free cellular spike protein is selectively cleaved into S1 and S2 subunits in a lysosomal-dependent manner. Importantly, we show that the pan-PAK inhibitor FRAX-486 restores ACE2 surface expression and suppresses infection by different SARS-CoV-2 strains. FRAX-486-treated Syrian hamsters exhibit significantly decreased lung viral load and alleviated pulmonary inflammation compared with untreated hamsters. In summary, our findings have identified novel pathways regulating viral entry, as well as therapeutic targets and candidate compounds for controlling the emerging strains of SARS-CoV-2 infection.
We developed an enzyme-linked immunosorbent assay (ELISA) using eukaryotically expressed E protein as the antigen (termed E-ELISA) to detect antibodies to tembusu virus (TMUV) in ducks. The E-ELISA did not react with antisera to other known pathogens, indicating the E protein is specific for recognizing anti-TMUV antibodies. Compared to the serum neutralization test, the specificity and sensitivity of the E-ELISA was 93.2 and 97.8%, respectively. Therefore, this E-ELISA is a sensitive and rapid method for detecting antibodies against TMUV in ducks.
SARS-CoV-2 inactivated vaccines have shown remarkable efficacy in clinical trials, especially in reducing severe illness and casualty. However, the waning of humoral immunity over time has raised concern over the durability of immune memory following vaccination. Thus, we conducted a nonrandomized trial among the healthcare workers (HCWs) to investigate the long-term sustainability of SARS-CoV-2-specific B cells and T cells stimulated by inactivated vaccines and the potential need for a third booster dose. Although neutralizing antibodies elicited by the standard two-dose vaccination schedule dropped from a peak of 29.3 arbitrary units (AU)/mL to 8.8 AU/mL 5 months after the second vaccination, spike-specific memory B and T cells were still detectable, forming the basis for a quick recall response. As expected, the faded humoral immune response was vigorously elevated to 63.6 AU/mL by 7.2 folds 1 week after the third dose along with abundant spike-specific circulating follicular helper T cells in parallel. Meanwhile, spike-specific CD4
The host intestinal microbiota has emerged as the third element in the interactions between hosts and enteric viruses, and potentially affects the infection processes of enteric viruses. However, the interaction of porcine enteric coronavirus with intestinal microorganisms during infection remains unclear. In this study, we used 16S-rRNA-based Illumina NovaSeq high-throughput sequencing to identify the changes in the intestinal microbiota of piglets mediated by porcine epidemic diarrhea virus (PEDV) infection and the effects of the alterations in intestinal bacteria on PEDV infection and its molecular mechanisms. The intestinal microbiota of PEDV-infected piglets had significantly less diversity than the healthy group and different bacterial community characteristics. Among the altered intestinal bacteria, the relative abundance of Clostridium perfringens was significantly increased in the PEDV-infected group. A strain of C. perfringens type A, named DQ21, was successfully isolated from the intestines of healthy piglets. The metabolites of swine C. perfringens type A strain DQ21 significantly enhanced PEDV replication in porcine intestinal epithelial cell clone J2 (IPEC-J2) cells, and PEDV infection and pathogenicity in suckling piglets. Palmitic acid (PA) was identified as one of those metabolites with metabolomic technology, and significantly enhanced PEDV replication in IPEC-J2 cells and PEDV infection and pathogenicity in suckling piglets. PA also increased the neutralizing antibody titer in the immune sera of mice. Furthermore, PA mediated the palmitoylation of the PEDV S protein, which improved virion stability and membrane fusion, thereby enhancing viral infection. Overall, our study demonstrates a novel mechanism of PEDV infection, with implications for PEDV pathogenicity.
ABSTRACT Here, we report the complete genome sequence of feline calicivirus (FCV) strain HRB-SS isolated in 2014 from a cat in Heilongjiang Province of northeastern China. The virus genome is 7,705 bases, excluding the poly(A) tail. This analysis will help to understand the genetic characteristics and evolution of FCV in China.
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