Bovine lactoferrin inhibits SARS-CoV-2 and SARS-CoV-1 by targeting the RdRp complex and alleviates viral infection in the hamster model.

Breast milk has been found to inhibit coronavirus infection, while the key components and mechanisms are unknown. We aimed to determine the components that contribute to the antiviral effects of breastmilk and explore their potential mechanism. Lactoferrin (Lf) and milk fat globule membrane (MFGM) inhibit SARS-CoV-2 related coronavirus GX_P2V and SARS-CoV-2 trVLP in vitro and block viral entry into cells. We confirmed that bovine lactoferrin (bLf) blocked the binding between human angiotensin-converting enzyme 2 (hACE2) and SARS-CoV-2 spike protein by combining receptor binding domain (RBD). Importantly, bLf inhibited RNA-dependent RNA polymerase (RdRp) activity of both SARS-CoV-2 and SARS-CoV in vitro in the nanomolar range. So far, no biological macromolecules have been reported to inhibit coronavirus RdRp. Our result indicated that bLf plays a major role in inhibiting viral replication rather than viral entry, which has been widely explored. bLf treatment reduced viral load in lungs and tracheae and alleviated pathological damage. Our study provides evidence that bLf prevents SARS-CoV-2 infection by combining SARS-CoV-2 spike protein RBD and inhibiting coronaviruses' RdRp activity, and may be a promising candidate for the treatment of COVID-19. This article is protected by copyright. All rights reserved.

Cepharanthine: A Promising Old Drug against SARS-CoV-2.

Recently, the inhibiting effects of a clinically approved drug Cepharanthine on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have attracted widespread attention and discussion. However, the public does not understand the relevant research progress very well. This paper aims to introduce a brief history of studies on the effects of cepharanthine against SARS-CoV-2, including "discovery of anti-SARS-CoV-2 activity of cepharanthine in vitro", "potential mechanisms of cepharanthine against SARS-CoV-2", "confirmation of cepharanthine's anti-SARS-CoV-2 activity in vivo", "potential approaches for improving the druggability of cepharanthine" and "clinical trials of cepharanthine treating SARS-CoV-2 infection". Taken together, cepharanthine is believed to be a promising old drug for coronavirus disease-19 (COVID-19) therapy.

COVID-19 vaccine development: milestones, lessons and prospects.

With the constantly mutating of SARS-CoV-2 and the emergence of Variants of Concern (VOC), the implementation of vaccination is critically important. Existing SARS-CoV-2 vaccines mainly include inactivated, live attenuated, viral vector, protein subunit, RNA, DNA, and virus-like particle (VLP) vaccines. Viral vector vaccines, protein subunit vaccines, and mRNA vaccines may induce additional cellular or humoral immune regulations, including Th cell responses and germinal center responses, and form relevant memory cells, greatly improving their efficiency. However, some viral vector or mRNA vaccines may be associated with complications like thrombocytopenia and myocarditis, raising concerns about the safety of these COVID-19 vaccines. Here, we systemically assess the safety and efficacy of COVID-19 vaccines, including the possible complications and different effects on pregnant women, the elderly, people with immune diseases and acquired immunodeficiency syndrome (AIDS), transplant recipients, and cancer patients. Based on the current analysis, governments and relevant agencies are recommended to continue to advance the vaccine immunization process. Simultaneously, special attention should be paid to the health status of the vaccines, timely treatment of complications, vaccine development, and ensuring the lives and health of patients. In addition, available measures such as mix-and-match vaccination, developing new vaccines like nanoparticle vaccines, and optimizing immune adjuvant to improve vaccine safety and efficacy could be considered.

Molnupiravir and Its Antiviral Activity Against COVID-19.

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 (ß-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.

Efficient disinfection of SARS-CoV-2-like coronavirus, pseudotyped SARS-CoV-2 and other coronaviruses using cold plasma induces spike protein damage.

Coronavirus disease 2019 (COVID-19) has become a worldwide public health emergency, and the high transmission of SARS-CoV-2 variants has raised serious concerns. Efficient disinfection methods are crucial for the prevention of viral transmission. Herein, pulse power-driven cold atmospheric plasma (CAP), a novel sterilization strategy, was found to potently inactivate SARS-CoV-2-like coronavirus GX_P2V, six strains of major epidemic SARS-CoV-2 variants and even swine coronavirus PEDV and SADS-CoV within 300 s (with inhibition rate more than 99%). We identified four dominant short-lived reactive species, ONOO-, 1O2, O2- and·OH, generated in response to CAP and distinguished their roles in the inactivation of GX_P2V and SARS-CoV-2 spike protein receptor binding domain (RBD), which is responsible for recognition and binding to human angiotensin-converting enzyme 2 (hACE2). Our study provides detailed evidence of a novel surface disinfection strategy for SARS-CoV-2 and other coronaviruses.

Understanding the Secret of SARS-CoV-2 Variants of Concern/Interest and Immune Escape.

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.