The cholesterol metabolite 27-hydroxycholesterol inhibits SARS-CoV-2 and is markedly decreased in COVID-19 patients
Alessandro Marcello,
Andrea Civra,
Rafaela Milan Bonotto,
Lais Nascimento Alves,
Sreejith Rajasekharan,
Chiara Giacobone,
Claudio Caccia,
Roberta Cavalli,
Marco Adami,
Paolo Brambilla,
David Lembo,
Giuseppe Poli,
Valerio Leoni
Affiliations
Alessandro Marcello
Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, 34149, Italy
Andrea Civra
Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Orbassano, Turin, 10043, Italy
Rafaela Milan Bonotto
Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, 34149, Italy
Lais Nascimento Alves
Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, 34149, Italy
Sreejith Rajasekharan
Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, 34149, Italy
Chiara Giacobone
Laboratory of Clinical Chemistry, Hospitals of Desio and Monza, ASST-Monza and Department of Medicine and Surgery, University of Milano-Bicocca, Monza, 20900, Italy
Claudio Caccia
Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, 20133, Italy
Roberta Cavalli
Department of Drug Science and Technology, University of Turin, Turin, Italy
Marco Adami
Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133, Italy
Paolo Brambilla
Laboratory of Clinical Chemistry, Hospitals of Desio and Monza, ASST-Monza and Department of Medicine and Surgery, University of Milano-Bicocca, Monza, 20900, Italy
David Lembo
Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Orbassano, Turin, 10043, Italy; Corresponding author.
Giuseppe Poli
Unit of General Pathology and Physiopathology, Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Orbassano, Turin, 10043, Italy; Corresponding author.
Valerio Leoni
Laboratory of Clinical Chemistry, Hospitals of Desio and Monza, ASST-Monza and Department of Medicine and Surgery, University of Milano-Bicocca, Monza, 20900, Italy
There is an urgent need to identify antivirals against the coronavirus SARS-CoV-2 in the current COVID-19 pandemic and to contain future similar emergencies early on. Specific side-chain cholesterol oxidation products of the oxysterols family have been shown to inhibit a large variety of both enveloped and non-enveloped human viral pathogens. Here we report on the in vitro inhibitory activity of the redox active oxysterol 27-hydroxycholesterol against SARS-CoV-2 and against one of the common cold agents HCoV-OC43 human coronavirus without significant cytotoxicity. Interestingly, physiological serum levels of 27-hydroxycholesterol in SARS-CoV-2 positive subjects were significantly decreased compared to the matched control group, reaching a marked 50% reduction in severe COVID-19 cases. Moreover, no correlation at all was observed between 24-hydroxycholesterol and 25-hydroxycholesterol serum levels and the severity of the disease. Opposite to that of 27-hydroxycholesterol was the behaviour of two recognized markers of redox imbalance, i.e. 7-ketocholesterol and 7β-hydroxycholesterol, whose serum levels were significantly increased especially in severe COVID-19. The exogenous administration of 27-hydroxycholesterol may represent in the near future a valid antiviral strategy in the worsening of diseases caused by present and emerging coronaviruses.
