Cyclosporine: an old weapon in the fight against coronaviruses

Abstract

Coronaviruses have been known to cause respiratory infections in humans and intestinal infections in other mammals. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 , is the seventh virus of the Coronaviridae family that is known to infect humans. Until 2002, four Coronaviruses infecting humans were described (HCoV-NL63, HCoV-229E, HCoV-OC43 and HKU1). These viruses caused only mild respiratory diseases in immunocompetent hosts. Since 2002, three highly pathogenic viruses from this family have been identified. SARS-CoV (also referred to as SARS-CoV-1) is an enveloped, positive-sense, single-stranded RNA virus which infects the epithelial cells within the lungs. The virus enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2) It infects humans, bats and palm civets It emerged in 2002-2003 with an approximate 10% mortality but limited transmissibility (approximately 8100 cases, R 0 <1) Infected persons develop influenza-like symptoms which may progress to pneumonia, acute respiratory distress syndrome (ARDS) and death from respiratory failure and multi-organ failure. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 in Saudi Arabia and was the second highly pathogenic virus of this family [6], yet with relatively low rate of transmission. MERS-CoV had even higher mortality than SARS-CoV (30%), but again was characterised by low transmissibility (approximately 2500 cases since 2012, R 0 <1) Typical MERS symptoms include fever, cough and shortness of breath. Pneumonia is common, but not always present. Gastrointestinal symptoms, including diarrhoea, have also been reported. Some laboratory-confirmed cases of MERS-CoV infection are reported as asymptomatic. Most of these asymptomatic cases have been detected following aggressive contact tracing of a laboratory-confirmed case. Dromedary camels are a major reservoir host for this virus. SARS-CoV-2 emerged in 2019 in Wuhan, China and is characterised by a much higher person-to-person transmissibility than SARS-CoV or MERS-CoV. The SARS-CoV-2 virus, responsible for COVID-19 disease, contains four main structural proteins. One of them, the S (spike) glycoprotein, a transmembrane protein, found in the outer portion of the virus, forms homotrimers binding with human ACE2 receptors of host cells The SARS CoV-2 S protein has significant homology with the SARS-CoV-1 equivalent protein However, the SARS CoV-2 S protein binds with higher affinity to ACE2 receptors [10] due to the presence of a furin-like cleavage site ( 682 RRAR/S 686 ) inserted in the S1/S2 protease cleavage site A considerable percentage of

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