Depletion of Host and Viral Sphingomyelin Impairs Influenza Virus Infection.

Influenza A virus (IAV) is a major human respiratory pathogen causing annual epidemics as well as periodic pandemics. A complete understanding of the virus pathogenesis and host factors involved in the viral lifecycle is crucial for developing novel therapeutic approaches. Sphingomyelin (SM) is the most abundant membrane sphingolipid. It preferentially associates with cholesterol to form distinct domains named lipid rafts. Sphingomyelinases, including acid sphingomyelinase (ASMase), catalyzes the hydrolysis of membrane SM and consequently transform lipid rafts into ceramide-enriched membrane platforms. In this study, we investigated the effect of SM hydrolysis on IAV propagation. Depleting plasma membrane SM by exogenous bacterial SMase (bSMase) impaired virus infection and reduced virus entry, whereas exogenous SM enhanced infection. Moreover, the depletion of virus envelope SM also reduced virus infectivity and impaired its attachment and internalization. Nonetheless, inhibition of ASMase by desipramine did not affect IAV infection. Similarly, virus replication was not impaired in Niemann-Pick disease type A (NPA) cells, which lack functional ASMase. IAV infection in A549 cells was associated with suppression of ASMase activity starting at 6 h post-infection. Our data reveals that intact cellular and viral envelope SM is required for efficient IAV infection. Therefore, SM metabolism can be a potential target for therapeutic intervention against influenza virus infection.

Seasonality of Respiratory Viral Infections: Will COVID-19 Follow Suit?

Respiratory viruses, including coronaviruses, are known to have a high incidence of infection during winter, especially in temperate regions. Dry and cold conditions during winter are the major drivers for increased respiratory tract infections as they increase virus stability and transmission and weaken the host immune system. The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in China in December 2020 and swiftly spread across the globe causing substantial health and economic burdens. Several countries are battling with the second wave of the virus after a devastating first wave of spread, while some are still in the midst of their first wave. It remains unclear whether SARS-CoV-2 will eventually become seasonal or will continue to circulate year-round. In an attempt to address this question, we review the current knowledge regarding the seasonality of respiratory viruses including coronaviruses and the viral and host factors that govern their seasonal pattern. Moreover, we discuss the properties of SARS-CoV-2 and the potential impact of meteorological factors on its spread.

COVID-19 Therapeutic Options Under Investigation.

Since its emergence in China in December 2019, COVID-19 has quickly spread around the globe causing a pandemic. Vaccination or the development of herd immunity seems the only way to slow down the spread of the virus; however, both are not achievable in the near future. Therefore, effective treatments to mitigate the burden of this pandemic and reduce mortality rates are urgently needed. Preclinical and clinical studies of potential antiviral and immunomodulatory compounds and molecules to identify safe and efficacious therapeutics for COVID-19 are ongoing. Two compounds, remdesivir, and dexamethasone have been so far shown to reduce COVID-19-associated death. Here, we provide a review of the potential therapeutic agents being considered for the treatment and management of COVID-19 patients.