Recent Developments in Anti-Severe Acute Respiratory Syndrome Coronavirus Chemotherapy

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in early 2003 to cause a very severe acute respiratory syndrome, which eventually resulted in a 10% case-fatality rate. Owing to excellent public health measures that isolated focus cases and their contacts, and the use of supportive therapies, the epidemic was suppressed to the point that further cases have not appeared since 2005. However, despite intensive research since then (over 3500 publications), it remains an untreatable disease. The potential for re-emergence of the SARS-CoV or a similar virus with unknown but potentially serious consequences remains high. This is due in part to the extreme genetic variability of RNA viruses such as the coronaviruses, the many animal reservoirs that seem to be able host the SARS-CoV in which reassortment or recombination events could occur and the ability coronaviruses have to transmit relatively rapidly from species to species in a short period of time. Thus, it seems prudent to continue to explore and develop antiviral chemotherapies to treat SARS-CoV infections. To this end, the various efficacious anti-SARS-CoV therapies recently published from 2007 to 2010 are reviewed in this article. In addition, compounds that have been tested in various animal models and were found to reduce virus lung titers and/or were protective against death in lethal models of disease, or otherwise have been shown to ameliorate the effects of viral infection, are also reported.

Anti-SARS coronavirus agents: a patent review (2008 – present)

“…It was first reported in Guangdong province of China and by July 2003 SARS spread to > 30 countries infecting 8,000 people and killing nearly 800 before being contained through public health measures [7]. SARS is caused by a novel coronavirus (CoV)--SARS coronavirus (SARS-CoV).…”

“…Popularly, 3CL pro and PL pro are still considered as a viable targets, along with some new alternatives, such as E protein (Orf4), M protein (Orf6), N protein (Orf9), Orf3a, RNA-dependent RNA polymerase (RdRp) and 5¢--3¢ helicase [7]. Vaccine development using polypeptides derived from structural or non-structural proteins to induce humoral or cell-mediated immunity has also been pursued.…”

Cell-based antiviral screening against coronaviruses: Developing virus-specific and broad-spectrum inhibitors

“…For replication to continue, these polyproteins must be cleaved by viral proteases, either 1 or 2 papain-like proteases (designated PL pro or PLP1/PLP2) and the 3C-like protease (3CL pro or M pro for main protease). This step in the replicative process has been the target of the most extensive work done to identify inhibitors for SARS-CoV replication (reviewed in Barnard & Kumaki, 2011). SARS-CoV PL pro is responsible for three cleavages while SARS-CoV 3CL pro cleaves the polyprotein at 11 sites (Figure 1).…”

Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors

“…[12] Though tremendous efforts have been made to develop inhibitors, therapeutic interventions for the continuous outbreaks of these deadly CoVs, are yet to reach the market. [13,14] While the origin of SARS dates back to early 2003, influenza has a century-old history of affecting humans. Influenza virus is an enveloped RNA virus that belongs to the orthomyxoviridae family.…”