Abstract
New pathogenic virus outbreaks, occurring with increasing regularity, are leading us to explore novel approaches, which will reduce the reliance on time-consuming vaccine modes to halt the outbreaks. The requirement is to find a universal approach to disarm any new and as yet unknown viruses as they appear. A promising approach could be targeting lipid membranes, which are common to all viruses and bacteria. The ongoing pandemic of severe acute respiratory syndrome-coronavirus 2 (SARS-COV-2) has reaffirmed the importance of interactions between components of the host cell plasma membrane and the virus envelope as a critical mechanism of infection. Metadichol®, a nano lipid emulsion, has been examined and shown to be a strong candidate to help stop the proliferation of SARS-COV-2. Naturally derived substances, such as long-chain saturated lipid alcohols, reduce the infectivity of various types of viruses, including coronaviruses such as SARS-COV-2, by modifying lipid-dependent attachment to human host cells. SARS-COV-2 uses the receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. Metadichol®, a nano lipid formulation of long-chain alcohols, has been shown to inhibit TMPRSS2 (EC50 96 ng/ml). Compared to the inhibitor camostat mesylate (EC50 26000 ng/ml), it is 270 times more potent. Additionally, Metadichol® is also a weak inhibitor of ACE2 at 31 µg/ml. Further a live virus assay in Caco2 cells, Metadichol® inhibited SARS-CoV-2 replication with an EC90 of 0.16 µg/ml.
Highlights
There is an increasing need to develop broadspectrum antimicrobial agents that can inactivate human pathogens, such as bacteria and viruses
For all practical purposes, it does not inhibit angiotensin-converting enzyme 2 (ACE2) (Table 7 and Figures 3 and 4) and inhibits transmembrane protease serine 2 (TMPRSS2) which is needed for the virus to bind to angiotensin-converting enzyme (ACE) 2
Inhibition of ACE, a blood pressure regulator, is crucial to mitigate COVID-19 infections, as Guan et al [26] validated that the single highest risk factor in infections is hypertension in 15% of the 1099 COVID-19 patients that participated in the study
Summary
There is an increasing need to develop broadspectrum antimicrobial agents that can inactivate human pathogens, such as bacteria and viruses. Rapid development of antimicrobial resistance in microorganisms has propelled the development of targeted drugs. The most recent trigger is the fear of a future pandemic caused by poorly studied novel virulent strains, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The ongoing COVID-19 pandemic caused by SARS-CoV-2 [1] has created global havoc within a few months of its emergence. The SARS-CoV-2 virus enters a host cell by interacting with the transmembrane protease serine 2 (TMPRSS2) [3], a serine protease, and the angiotensin-converting enzyme 2 (ACE2) present on the host cell [4]. Inhibiting TMPRSS2 is the key to blocking the virus from binding to ACE2, hindering the mechanism underlying its entry into the host cell
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