Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome: Current Therapeutic Options and Potential Targets for Novel Therapies

Abstract

No specific antivirals are currently available for two emerging infectious diseases, Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). A literature search covering pathogenesis, clinical features and therapeutics, clinically developed drugs for repurposing and novel drug targets was performed. This review presents current knowledge on the epidemiology, pathogenesis and clinical features of the SARS and MERS coronaviruses. The rationale for and outcomes with treatments used for SARS and MERS is discussed. The main focus of the review is on drug development and the potential that drugs approved for other indications provide for repurposing. The drugs we discuss belong to a wide range of different drug classes, such as cancer therapeutics, antipsychotics, and antimalarials. In addition to their activity against MERS and SARS coronaviruses, many of these approved drugs have broad-spectrum potential and have already been in clinical use for treating other viral infections. A wealth of knowledge is available for these drugs. However, the information in this review is not meant to guide clinical decisions, and any therapeutic described here should only be used in context of a clinical trial. Potential targets for novel antivirals and antibodies are discussed as well as lessons learned from treatment development for other RNA viruses. The article concludes with a discussion of the gaps in our knowledge and areas for future research on emerging coronaviruses.

Drug Repurposing for Viral Infectious Diseases: How Far Are We?

“…Indeed, a targeted drug combination approach resulted in the identification of two sets of three-drug cocktails (i.e., toremifene-mefloquine-posaconazole and toremifeneclarithromycin-posaconazole, all previously identified by DR) that act synergistically in an EBOV entry-inhibition assay and at concentrations achievable in humans [44]. [45]. Thus, CoVs represent a huge threat to public health; in this scenario, the search for effective therapeutic strategies is a priority for global public health management.…”

Repurposing host-based therapeutics to control coronavirus and influenza virus

“…Imatinib is used as an anticancer agent to reduce CML-related disease progression and death [52,53]. Imatinib is also an endosomal membrane fusion inhibitor capable of inhibiting SARS-CoV and MERS-CoV infection with EC 50 values of 9.82 and 17.69 mM, respectively [2,54]. Pretreatment with imatinib reduces 1000-fold MERS-CoV and SARS-CoV production in Vero cells and is safe to Vero cells (CC 50 value >100 mM) [54].…”

“…Endosomal acidification facilitates membrane fusion between endosomes and virions for viral entry. Imatinib, an FDA-approved agent, inhibits CoV fusion with the endosomal membrane in vitro [2,54]; thus, the in vivo efficacy of imatinib in the control of viral infection needs to be determined in an animal model. Treatment of animals with the v-ATPase inhibitors SaliPhe or diphyllin reduces acidification and suppresses viral infection; and packing with nanoparticles helps to increase the efficacy of these inhibitors in controlling viral infection with tolerable adverse effects in animals.…”

“…SARS and MERS have been well recognized globally owing to their outbreaks of severe infection [1]. However, the lack of effective therapeutic drugs to control SARS and MERS means that high morbidity and mortality rates have not reduced [2]. In addition to high morbidity and mortality, the emergence of new wide-host-range viral members, the potential domestic animal adaptation and the difficulty in identifying intermediate hosts are major concerns in the control of CoV infection.…”

Repurposing approved drugs on the pathway to novel therapies

“…The bioflavonoid rutin inhibits norovirus . Quinine and other antimalarials have been suggested for flaviviruses such as Dengue and Zika as well as the coronaviruses MERS/SARS . The clinical future of these treatments will depend on whether the side effects during short term administration are acceptable.…”