Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA has been detected in human breastmilk, infants' safety with breastmilk feeding is of great concern for women with coronavirus disease 2019 (COVID-19). 1 It is known that milk has antiviral properties. 2 However, little is known about the antiviral property of human breastmilk to SARS-CoV-2 and its related pangolin coronavirus (GX_P2V). Here we present for the first time that whey protein from human breastmilk effectively inhibited both SARS-CoV-2 and GX_P2V by blocking viral attachment and viral replication at entry and even post entry. Moreover, human whey protein inhibited infectious virus production, as proved by the plaque assay. We found that whey protein from different species, such as cow and goat, also showed anti-coronavirus properties. Commercial bovine formula milk also showed similar anti-SARS-CoV-2 activity. Firstly, healthy human breastmilk samples collected in 2017 and stored properly at −80°C were tested for their potential effects on SARS-CoV-2 infection. Mothers provided informed consent. This study was approved by the ethics committees of the Medical Center and all samples were anonymized. The skimmed breastmilk was obtained after removal of the lipid fraction. Vero E6 cells were infected with a mixture of SARS-CoV-2 pseudovirus (650 TCID 50 /well) and human breastmilk (4 mg/ ml). Human breastmilk from eight donors showed a significant inhibition of more than 98% of the SARS-CoV-2 pseudovirus. As reported recently, a SARS-CoV-2-related pangolin coronavirus model (GX_P2V) 3 shares 92.2% amino acid identity in spike protein with SARS-CoV-2, which is a suitable model for SARS-CoV-2 infection research. We utilized GX_P2V (MOI: 0.01 in Vero E6 cells) as the model to study the effect of breastmilk on viral infection and also found similar results (Fig. 1a). The inhibition is concentration dependent with an EC 50 of 0.13 mg/ml of total protein (Fig. 1b and Supplementary Fig. S1) in the SARS-CoV-2 pseudovirus model. Consistent with the SARS-CoV-2 study, the GX_P2V model also showed inhibition with an EC 50 of about 0.5 mg/ml of total protein (Fig. 1c and Supplementary Fig. S2). Interestingly, human breastmilk did not show any cytotoxicity to Vero E6 cells (CC 50 > 3 mg/ml), and even promoted cell proliferation. These results indicated that human breastmilk showed high anti-SARS-CoV-2 and anti-GX_P2V property, but limited cytotoxicity to Vero E6 cells. We then assessed the impact of human breastmilk on infectious virus production in Vero E6. RT-qPCR analysis of the GX_P2V virus from supernatant showed that even 0.16 mg/ml of breastmilk significantly blocked viral production (Fig. 1d). Western blot of viral nucleoprotein also showed similar results (Fig. 1e). To investigate the infectious virus, we performed plaque assay. As shown in Fig. 1f, the plaque assays showed that live viruses were significantly lower in breastmilk treatment compared to the control group, which confirmed that

Since the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human breastmilk, little is known about the antiviral property of human breastmilk to SARS-CoV-2 and its related pangolin coronavirus (GX_P2V). Here we present for the first time that whey protein from human breastmilk effectively inhibited both SARS-CoV-2 and GX_P2V by blocking viral attachment, entry and even post-entry viral replication. Moreover, human whey protein inhibited infectious virus production proved by the plaque assay. We found that whey protein from different species such as cow and goat also showed anti-coronavirus properties. And commercial bovine milk also showed similar activity. Interestingly, the main antimicrobial components of breastmilk, such as Lactoferrin and IgA antibody, showed limited anti-coronavirus activity, indicating that other factors of breastmilk may play the important anti-coronavirus role. Taken together, we reported that whey protein inhibits SARS-CoV-2 and its related virus of GX_P2V. These results rule out whey protein as a direct-acting inhibitor of SARS-CoV-2 and GX_P2V infection and replication and further investigation of its molecular mechanism of action in the context of COVID-19.

Targeting the interaction between severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)-receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2) is believed to be an effective strategy for drug design to inhibit the infection of SARS-CoV-2. Herein, several ultrashort peptidase inhibitors against the RBD–ACE2 interaction were obtained by a computer-aided approach based on the RBD-binding residues on the protease domain (PD) of ACE2. The designed peptides were tested on a model coronavirus GX_P2V, which has 92.2 and 86% amino acid identity to the SARS-CoV-2 spike protein and RBD, respectively. Molecular dynamics simulations and binding free energy analysis predicted a potential binding pocket on the RBD of the spike protein, and this was confirmed by the specifically designed peptides SI5α and SI5α-b. They have only seven residues, showing potent antiviral activity and low cytotoxicity. Enzyme-linked immunosorbent assay result also confirmed their inhibitory ability against the RBD–ACE2 interaction. The ultrashort peptides are promising precursor molecules for the drug development of Corona Virus Disease 2019, and the novel binding pocket on the RBD may be helpful for the design of RBD inhibitors or antibodies against SARS-CoV-2.

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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.