Metadichol®: A Novel Nanolipid Formulation That Inhibits SARS-CoV-2 and a Multitude of Pathological Viruses In Vitro

Biomed Res Int. 2022 Jan 15;2022:1558860. doi: 10.1155/2022/1558860. eCollection 2022.

Abstract

Increasing outbreaks of new pathogenic viruses have promoted the exploration of novel alternatives to time-consuming vaccines. Thus, it is necessary to develop a universal approach to halt the spread of new and unknown viruses as they are discovered. One such promising approach is to target lipid membranes, which are common to all viruses and bacteria. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has reaffirmed the importance of interactions between the virus envelope and the host cell plasma membrane as a critical mechanism of infection. Metadichol®, a nanolipid emulsion of long-chain alcohols, has been demonstrated as a strong candidate that inhibits the proliferation of SARS-CoV-2. Naturally derived substances, such as long-chain saturated lipid alcohols, reduce viral infectivity, including that of coronaviruses (such as SARS-CoV-2) by modifying their lipid-dependent attachment mechanism to human host cells. The receptor ACE2 mediates the entry of SARS-CoV-2 into the host cells, whereas the serine protease TMPRSS2 primes the viral S protein. In this study, Metadichol® was found to be 270 times more potent an inhibitor of TMPRSS2 (EC50 = 96 ng/mL) than camostat mesylate (EC50 = 26000 ng/mL). Additionally, it inhibits ACE with an EC50 of 71 ng/mL, but it is a very weak inhibitor of ACE2 at an EC50 of 31 μg/mL. Furthermore, the live viral assay performed in Caco-2 cells revealed that Metadichol® inhibits SARS-CoV-2 replication at an EC90 of 0.16 μg/mL. Moreover, Metadichol® had an EC90 of 0.00037 μM, making it 2081 and 3371 times more potent than remdesivir (EC50 = 0.77 μM) and chloroquine (EC50 = 1.14 μM), respectively.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • COVID-19 Drug Treatment
  • Cell Line
  • Chlorocebus aethiops
  • Esters / pharmacology
  • Fatty Alcohols / pharmacology*
  • Guanidines / pharmacology
  • Humans
  • Lipid Metabolism / physiology
  • Lipids / chemistry
  • Nanoparticle Drug Delivery System / pharmacology*
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / metabolism
  • SARS-CoV-2 / pathogenicity
  • Serine Endopeptidases / drug effects
  • Serine Endopeptidases / metabolism
  • Serine Proteases / metabolism
  • Serine Proteinase Inhibitors / pharmacology
  • Spike Glycoprotein, Coronavirus / metabolism
  • Vero Cells
  • Virus Attachment / drug effects
  • Virus Internalization / drug effects
  • Viruses / drug effects*

Substances

  • Antiviral Agents
  • Esters
  • Fatty Alcohols
  • Guanidines
  • Lipids
  • Nanoparticle Drug Delivery System
  • Serine Proteinase Inhibitors
  • Spike Glycoprotein, Coronavirus
  • camostat
  • policosanol
  • Serine Proteases
  • Serine Endopeptidases
  • TMPRSS2 protein, human