Explore the vast range of titles available.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a major worldwide public health threat and economic burden. The pandemic is still ongoing and the SARS-CoV-2 variants are still emerging constantly, resulting in an urgent demand for new drugs to treat this disease. Molnupiravir, a biological prodrug of NHC (β-D-N(4)-hydroxycytidine), is a novel nucleoside analogue with a broad-spectrum antiviral activity against SARS-CoV, SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), influenza virus, respiratory syncytial virus (RSV), bovine viral diarrhea virus (BVDV), hepatitis C virus (HCV) and Ebola virus (EBOV). Molnupiravir showed potent therapeutic and prophylactic activity against multiple coronaviruses including SARS-CoV-2, SARS-CoV, and MERS-CoV in animal models. In clinical trials, molnupiravir showed beneficial effects for mild to moderate COVID-19 patients with a favorable safety profile. The oral bioavailability and potent antiviral activity of molnupiravir highlight its potential utility as a therapeutic candidate against COVID-19. This review presents the research progress of molnupiravir starting with its discovery and synthesis, broad-spectrum antiviral effects, and antiviral mechanism. In addition, the preclinical studies, antiviral resistance, clinical trials, safety, and drug tolerability of molnupiravir are also summarized and discussed, aiming to expand our knowledge on molnupiravir and better deal with the COVID-19 epidemic.

Cepharanthine, a natural bisbenzylisoquinoline (BBIQ) alkaloid isolated from the plant Stephania Cephalantha Hayata, is the only bisbenzylisoquinoline alkaloid approved for human use and has been used in the clinic for more than 70 years. Cepharanthine has a variety of medicinal properties, including signaling pathway inhibitory activities, immunomodulatory activities, and antiviral activities. Recently, cepharanthine has been confirmed to greatly inhibit SARS-CoV-2 infection. Therefore, we aimed to describe the pharmacological properties and mechanisms of cepharanthine, mainly including antitumor, anti-inflammatory, anti-pathogen activities, inhibition of bone resorption, treatment of alopecia, treatment of snake bite, and other activities. At the same time, we analyzed and summarized the potential antiviral mechanism of cepharanthine and concluded that one of the most important anti-viral mechanisms of cepharanthine may be the stability of plasma membrane fluidity. Additionally, we explained its safety and bioavailability, which provides evidence for cepharanthine as a potential drug for the treatment of a variety of diseases. Finally, we further discuss the potential new clinical applications of cepharanthine and provide direction for its future development.

The global pandemic of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), places a heavy burden on global public health. Four SARS-CoV-2 variants of concern including B.1.1.7, B.1.351, B.1.617.2, and P.1, and two variants of interest including C.37 and B.1.621 have been reported to have potential immune escape, and one or more mutations endow them with worrisome epidemiologic, immunologic, or pathogenic characteristics. This review introduces the latest research progress on SARS-CoV-2 variants of interest and concern, key mutation sites, and their effects on virus infectivity, mortality, and immune escape. Moreover, we compared the effects of various clinical SARS-CoV-2 vaccines and convalescent sera on epidemic variants, and evaluated the neutralizing capability of several antibodies on epidemic variants. In the end, SARS-CoV-2 evolution strategies in different transmission stages, the impact of different vaccination strategies on SARS-CoV-2 immune escape, antibody therapy strategies and COVID-19 epidemic control prospects are discussed. This review will provide a systematic and comprehensive understanding of the secret of SARS-CoV-2 variants of interest/concern and immune escape.

Coxsackieviruses, a genus of enteroviruses in the small RNA virus family, cause fatal infectious diseases in humans. Thus far, there are no approved drugs to prevent these diseases. Human milk contains various biologically active components against pathogens. Currently, the potential activity of breast milk components against the coxsackievirus remains unclear. In our study, the inhibitory effect of 16 major human milk components was tested on coxsackievirus class A type 9 isolate (CV-A9), BUCT01; 2’-Fucosyllactose (2’-FL) was identified to be effective. Time-of-addition, attachment internalisation assays, and the addition of 2’-FL at different time points were applied to investigate its specific role in the viral life cycle. Molecular docking was used to predict 2’-FL’s specific cellular targets. The initial screening revealed a significant inhibitory effect (99.97%) against CV-A9 with 10 mg/mL 2’-FL, with no cytotoxicity observed. Compared with the control group, 2’-FL blocked virus entry (85%) as well as inhibited viral attachment (48.4%) and internalisation (51.3%), minimising its infection in rhabdomyosarcoma (RD) cells. The cell pre-incubation with 2’-FL exhibited significant inhibition (73.2–99.9%). Extended incubation between cells with 2’-FL reduced CV-A9 infection (93.9%), suggesting that 2’-FL predominantly targets cells to block infection. Molecular docking results revealed that 2’-FL interacted with the attachment receptor αvβ6 and the internalisation receptor FCGRT and β2M with an affinity of −2.14, −1.87, and −5.43 kcal/mol, respectively. This study lays the foundation for using 2’-FL as a food additive against CV-A9 infections.

Human enteroviruses are important pathogens of hand-foot-and-mouth disease, poliomyelitis, and encephalitis, etc., posing substantial global health burdens with no specific approved therapeutics. While traditional Chinese medicine (TCM) has demonstrated antiviral potential during the COVID-19 pandemic, its efficacy and pharmacodynamic material basis against enteroviruses remains underexplored. Here, we systematically characterized the broad-spectrum anti-enterovirus activity of Huashi Baidu Formula (HSBDF), a clinically approved TCM for COVID-19, and identified three flavonoid compounds as its active components responsible for this antiviral effect. Transcriptomics analysis revealed that HSBDF attenuated CV-A9-induced inflammation by modulating MAPK and NF-κB signaling pathways. High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) analysis identified 152 chemical compounds in HSBDF, among which three flavonoids—velutin, isorhamnetin, and (−)-epicatechin gallate—exhibited potent pan-enteroviral inhibition. Mechanistically, these compounds suppressed the activity of 3C proteases in enteroviruses, while concurrently attenuating CV-A9-induced upregulation of IL-6, TNF-α, MCP-1, and COX-2. Utilizing a BALB/c young mouse model, it was demonstrated that the HSBDF and its compound velutin effectively suppressed viral replication in vivo. Collectively, this study advances TCM-based strategies for enterovirus therapy exemplified by HSBDF and highlights flavonoid scaffolds as promising candidates for developing broad-spectrum anti-enteroviral agents.

During the global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pregnant and lactating women are at higher risk of infection. The potential of viral intrauterine transmission and vertical transmission by breastfeeding has raised wide concerns. Breastmilk is rich in nutrients that contribute to infant growth and development, and reduce the incidence rate of infant illness and death, as well as inhibit pathogens significantly, and protect infants from infection. Although it is controversial whether mothers infected with COVID-19 should continue to breastfeed, many countries and international organizations have provided recommendations and guidance for breastfeeding. This review presents the risks and benefits of breastfeeding for mothers infected with COVID-19, and the reasons for the absence of SARS-CoV-2 active virus in human milk. In addition, the antiviral mechanisms of nutrients in breastmilk, the levels of SARS-CoV-2 specific antibodies in breastmilk from COVID-19 infected mothers and vaccinated mothers are also summarized and discussed, aiming to provide some support and recommendations for both lactating mothers and infants to better deal with the COVID-19 pandemic.

Since the start of the coronavirus disease 2019 (COVID‐19) pandemic, new variants of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) have emerged, accelerating the spread of the virus. Omicron was defined by the World Health Organization in November 2021 as the fifth “variant of concern” after Alpha, Beta, Gamma, and Delta. In recent months, Omicron has become the main epidemic strain. Studies have shown that Omicron carries more mutations than Alpha, Beta, Gamma, Delta, and wild‐type, facilitating immune escape and accelerating its transmission. This review focuses on the Omicron variant's origin, transmission, main biological features, subvariants, mutations, immune escape, vaccination, and detection methods. We also discuss the appropriate preventive and therapeutic measures that should be taken to address the new challenges posed by the Omicron variant. This review is valuable to guide the surveillance, prevention, and development of vaccines and other therapies for Omicron variants. It is desirable to develop a more efficient vaccine against the Omicron variant and take more effective measures to constrain the spread of the epidemic and promote public health. In this article, we described the discovery of the Omicron variant, biological characteristics of the Omicron variant, immune escape, mutations, patients’ clinical features, vaccination, detection methods, treatment with drugs and neutralizing antibodies, and protective measures taken. It is desirable to develop a more efficient vaccine against the Omicron variant and take more effective measures to contain the spread of the epidemic and promote public health.