• Functional landscape of SARS-CoV-2 cellular restriction

      Martin-Sancho, Laura; Lewinski, Mary K; Pache, Lars; Stoneham, Charlotte A; Yin, Xin; Becker, Mark E; Pratt, Dexter; Churas, Christopher; Rosenthal, Sara B; Liu, Sophie; et al. (Cell Press, 2021-04-13)
      A deficient interferon (IFN) response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been implicated as a determinant of severe coronavirus disease 2019 (COVID-19). To identify the molecular effectors that govern IFN control of SARS-CoV-2 infection, we conducted a large-scale gain-of-function analysis that evaluated the impact of human IFN-stimulated genes (ISGs) on viral replication. A limited subset of ISGs were found to control viral infection, including endosomal factors inhibiting viral entry, RNA binding proteins suppressing viral RNA synthesis, and a highly enriched cluster of endoplasmic reticulum (ER)/Golgi-resident ISGs inhibiting viral assembly/egress. These included broad-acting antiviral ISGs and eight ISGs that specifically inhibited SARS-CoV-2 and SARS-CoV-1 replication. Among the broad-acting ISGs was BST2/tetherin, which impeded viral release and is antagonized by SARS-CoV-2 Orf7a protein. Overall, these data illuminate a set of ISGs that underlie innate immune control of SARS-CoV-2/SARS-CoV-1 infection, which will facilitate the understanding of host determinants that impact disease severity and offer potential therapeutic strategies for COVID-19.
    • Novel Insights Into Immune Systems of Bats

      Banerjee, A.; Baker, M.L.; Kulcsar, K. (Frontiers Media S.A., 2020)
      In recent years, viruses similar to those that cause serious disease in humans and other mammals have been detected in apparently healthy bats. These include filoviruses, paramyxoviruses, and coronaviruses that cause severe diseases such as Ebola virus disease, Marburg haemorrhagic fever and severe acute respiratory syndrome (SARS) in humans. The evolution of flight in bats seem to have selected for a unique set of antiviral immune responses that control virus propagation, while limiting self-damaging inflammatory responses. Here, we summarize our current understanding of antiviral immune responses in bats and discuss their ability to co-exist with emerging viruses that cause serious disease in other mammals. We highlight how this knowledge may help us to predict viral spillovers into new hosts and discuss future directions for the field. Copyright 2020 The Authors.
    • Ramatroban for chemoprophylaxis and treatment of COVID-19: David takes on Goliath.

      Chiang, Kate C; Rizk, John G; Nelson, Deanna J; Krishnamurti, Lakshmanan; Subbian, Selvakumar; Imig, John D; Khan, Imran; Reddy, Srinivasa T; Gupta, Ajay (Taylor and Francis Inc., 2022-02-22)
      In COVID-19 pneumonia, there is a massive increase in fatty acid levels and lipid mediators with a predominance of cyclooxygenase metabolites, notably TxB2 ≫ PGE2 > PGD2 in the lungs, and 11-dehydro-TxB2, a TxA2 metabolite, in the systemic circulation. While TxA2 stimulates thromboxane prostanoid (TP) receptors, 11-dehydro-TxB2 is a full agonist of DP2 (formerly known as the CRTh2) receptors for PGD2. Anecdotal experience of using ramatroban, a dual receptor antagonist of the TxA2/TP and PGD2/DP2 receptors, demonstrated rapid symptomatic relief from acute respiratory distress and hypoxemia while avoiding hospitalization.