COVID-19 global pandemic planning: Dry heat incubation and ambient temperature fail to consistently inactivate SARS-CoV-2 on N95 respirators.

The ongoing pandemic of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has placed a substantial strain on the supply of personal protective equipment, particularly the availability of N95 respirators for frontline healthcare personnel. These shortages have led to the creation of protocols to disinfect and reuse potentially contaminated personal protective equipment. A simple and inexpensive decontamination procedure that does not rely on the use of consumable supplies is dry heat incubation. Although reprocessing with this method has been shown to maintain the integrity of N95 respirators after multiple decontamination procedures, information on the ability of dry heat incubation to inactivate SARS-CoV-2 is largely unreported. Here, we show that dry heat incubation does not consistently inactivate SARS-CoV-2-contaminated N95 respirators, and that variation in experimental conditions can dramatically affect viability of the virus. Furthermore, we show that SARS-CoV-2 can survive on N95 respirators that remain at room temperature for at least five days. Collectively, our findings demonstrate that dry heat incubation procedures and ambient temperature for five days are not viable methods for inactivating SARS-CoV-2 on N95 respirators for potential reuse. We recommend that decontamination procedures being considered for the reuse of N95 respirators be validated at each individual site and that validation of the process must be thoroughly conducted using a defined protocol.

The iminosugars celgosivir, castanospermine and UV-4 inhibit SARS-CoV-2 replication.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an unprecedented challenge for health care and the global economy. Repurposing drugs that have shown promise in inhibiting other viral infections could allow for more rapid dispensation of urgently needed therapeutics. The Spike protein of SARS-CoV-2 is extensively glycosylated with 22 occupied N glycan sites and is required for viral entry. In other glycosylated viral proteins, glycosylation is required for interaction with calnexin and chaperone-mediated folding in the endoplasmic reticulum, and prevention of this interaction leads to unfolded viral proteins and thus inhibits viral replication. As such, we investigated two iminosugars, celgosivir, a prodrug of castanospermine, and UV-4, or N-(9-methoxynonyl)-1-deoxynojirimycin, a deoxynojirimycin derivative. Iminosugars are known inhibitors of the α-glucosidase I and II enzymes and were effective at inhibiting authentic SARS-CoV-2 viral replication in a cell culture system. Celgosivir prevented SARS-CoV-2-induced cell death and reduced viral replication and Spike protein levels in a dose-dependent manner in culture with Vero E6 cells. Castanospermine, the active form of celgosivir, was also able to inhibit SARS-CoV-2, confirming the canonical castanospermine mechanism of action of celgosivir. The monocyclic UV-4 also prevented SARS-CoV-2-induced death and reduced viral replication after 24 h of treatment, although the reduction in viral copies was lost after 48 h. Our findings suggest that iminosugars should be urgently investigated as potential SARS-CoV-2 inhibitors.