Clinical assessment of SARS-CoV-2 infectivity by rapid antigen test compared with virus isolation.

Although real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) remains as a golden standard for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it can not be easily expanded to large-scaled screening during outbreaks, and the positive results do not necessarily correlate with infectious status of the identified subjects. In this study, the performance of Vstrip® RV2 COVID-19 Antigen Rapid Test (RAT) and its correlation with virus infectivity was examined by virus culture using 163 sequential respiratory specimens collected from 26 SARS-CoV-2 infected patients. When the presence of cytopathic effects (CPE) in cell culture was used as a reference method for virus infectivity, the sensitivity, specificity and accuracy of Vstrip® RV2 COVID-19 Antigen Rapid Test was 96.43%, 89.63%, and 90.8%, respectively. The highest Ct value was 27.7 for RdRp gene and 25.79 for E gene within CPE-positive samples, and the highest Ct value was 31.9 for RdRp gene and 29.1 for E gene within RAT positive samples. When the Ct values of specimens were below 25, the CPE and RAT results had high degree of consistency. We concluded that the RAT could be a great alternative method for determining the infectious potential of individuals with high viral load.

Microwave resonant absorption of SARS-CoV-2 viruses.

Low power microwave can effectively deactivate influenza type A virus through the nonthermal structure-resonant energy transfer effect, at a frequency matching the confined-acoustic dipolar mode frequency of the virus. Currently, aerosol is considered the major route for SARS-CoV-2 transmission. For the potential microwave-based sterilization, the microwave-resonant frequency of SARS-CoV-2 must be unraveled. Here we report a microwave absorption spectroscopy study of the SARS-CoV-2 and HCoV-229E viruses through devising a coplanar-waveguide-based sensor. Noticeable microwave absorption can be observed, while we identified the resonant frequencies of the 1st and 2nd dipolar modes of SARS-CoV-2 virus as 4 and 7.5 GHz respectively. We further found that the resonant frequencies are invariant to the virus titer, and we also studied the microwave absorption of HCoV-229E in weak acidity medium to simulate the common pH value in fluid secretion. Our results suggest the possible radiation frequency for the recently proposed microwave sterilization devices to inactivate SARS-CoV-2 virus through a nonthermal mechanism so as to control the disease transmission in the post-pandemic era.

Neutralizing Monoclonal Antibodies Inhibit SARS-CoV-2 Infection through Blocking Membrane Fusion.

Most of SARS-CoV-2 neutralizing antibodies (nAbs) targeted the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, mutations at RBD sequences found in the emerging SARS-CoV-2 variants greatly reduced the effectiveness of nAbs. Here we showed that four nAbs, S2-4D, S2-5D, S2-8D, and S2-4A, which recognized a conserved epitope in the S2 subunit of the S protein, can inhibit SARS-CoV-2 infection through blocking the S protein-mediated membrane fusion. Notably, these four nAbs exhibited broadly neutralizing activity against SARS-CoV-2 Alpha, Gamma, Delta, and Epsilon variants. Antisera collected from mice immunized with the identified epitope peptides of these four nAbs also exhibited potent virus neutralizing activity. Discovery of the S2-specific nAbs and their unique antigenic epitopes paves a new path for development of COVID-19 therapeutics and vaccines. IMPORTANCE The spike (S) protein on the surface of SARS-CoV-2 mediates receptor binding and virus-host cell membrane fusion during virus entry. Many neutralizing antibodies (nAbs), which targeted the receptor binding domain (RBD) of S protein, lost the neutralizing activity against the newly emerging SARS-CoV-2 variants with sequence mutations at the RBD. In contrast, the nAb against the highly conserved S2 subunit, which plays the key role in virus-host cell membrane fusion, was poorly discovered. We showed that four S2-specific nAbs, S2-4D, S2-5D, S2-8D, and S2-4A, inhibited SARS-CoV-2 infection through blocking the S protein-mediated membrane fusion. These nAbs exhibited broadly neutralizing activity against Alpha, Gamma, Delta, and Epsilon variants. Antisera induced by the identified epitope peptides also possessed potent neutralizing activity. This work not only unveiled the S2-specific nAbs but also discovered an immunodominant epitope in the S2 subunit that can be rationally designed as the broad-spectrum vaccine against the SARS-like coronaviruses.

A siRNA targets and inhibits a broad range of SARS-CoV-2 infections including Delta variant.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has altered the trajectory of the COVID-19 pandemic and raised some uncertainty on the long-term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS-CoV-2 variants is imperative. We, here, have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS-CoV-2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma, and Epsilon, at picomolar ranges of IC50 in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by cotreatment in K18-hACE2-transgenic mice, accompanied by a significant prevention of virus-associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggest that C6G25S provides an alternative and effective approach to combating the COVID-19 pandemic.