In September 2012, a novel coronavirus (NCoV) was discovered in the Middle East in a 49 year-old Qatari man with travel history to Saudi Arabia prior to onset of illness. From April 2012 to February 2013, a total of 13 people from Jordan, Saudi Arabia, Qatar, and the United Kingdom were confirmed to have an infection caused by the novel coronavirus, and 7 of the infected have died. There are no specific treatment for illnesses caused by the novel coronavirus. Medical care is supportive and to help relieve symptoms.
Before this novel coronavirus 2012, the human coronaviruses (HCoV) OC43 and 229E are common causes of upper respiratory tract infections. Severe diseases were rare, however, until the emergence of the severe acute respiratory syndrome (SARS)-CoV in 2003. Since then, other novel CoV (NL63 and HKU1) have been described, and they have caused respiratory infections worldwide.
Generally, the viral loads of SARS-CoV collected at different anatomical sites correlate with the severity of symptoms and mortality. Shedding of SARS-CoV peaks at day 10 after the onset of symptoms, which theoretically allows ample time for antiviral treatment. The disease is characterized by uncontrolled replication of the virus and a prominent pro-inflammatory response. No randomized controlled trials with a specific anti-coronavirus agent have been conducted with respect to coronavirus treatment or prophylaxis. Reports using historical matched controls have suggested that treatment with interferon alfacon-1 (a synthetic interferon) combined with steroid, protease inhibitors together with ribavirin, or convalescent plasma containing neutralizing antibody, could be useful for the coronavirus symptoms of ease. Prophylaxis with interferon or hyperimmune globulin may be considered for unprotected exposure. The role of immunomodulators to decrease excessive inflammation remains elusive. Other non-SARS-CoV infections are generally milder in immunocompetent hosts, and scientific data on antiviral treatment of these coronaviruses are scarce.
Traditionally, there were no effective antiviral agents for coronaviruses and initial efforts focused on the use of currently available drugs, either conventional antiviral agents or non-antivirals with inhibitory effects on SARS-CoV. When SARS-CoV was better characterized in terms of virology and pathogenesis, attempts were made to target specific pathways or viral molecules using novel compounds. Another approach to treatment was the use of agents that augment the immune system or provide specific antibodies using passive immunization. It has to be noted that none of the potential antiviral agents has undergone randomized controlled clinical trials to assess their efficacies.
|Viral targets||Currently available drugs for human use||Investigational agents|
|Viral entry and fusion||Chloroquine||Convalescent plasma*, monoclonal antibodies, peptides representing different regions of ACE2, luteolin, other small molecules, peptides targeting S protein|
|Viral replication||Chloroquine||Calpain inhibitors|
|Viral protease||Protease inhibitors (lopinavir/ritonavir* and nelfinavir)||Quercetin|
|Viral RNA synthesis and gene expression||Ribavirin* and indomethacin||siRNA|
|Immunomodulation||Interferon alfacon-1*||Interferon-α and interferon-β|
|Unknown or other mechanisms||Nitric oxide*, niclosamide and reserpine||Glycyrrhizin, baicalin, valinomycin, nitric oxide donors (e.g. S-nitroso-N-acetylpenicillamine)|
|Comment: *Have been used in human subjects for the treatment of infection.|
Studies of antiviral treatment against coronaviruses other than SARS-CoV have been scarce. There have not been clinical trials on treatment of infections caused by HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1. Limited in vitro data suggested that intravenous immunoglobulins, heptad repeat 2 peptide, siRNA and some other chemicals may have inhibitory activities on HCoV-NL63, and saikosaponins (a group of oleanane derivatives from certain medicinal plants) are inhibitory to HCoV-229E.