Recent Aspects on the Pathogenesis Mechanism, Animal Models and Novel Therapeutic Interventions for Middle East Respiratory Syndrome Coronavirus Infections

Abstract

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging zoonotic virus considered as one of the major public threat with a total number of 2 298 laboratory-confirmed cases and 811 associated deaths reported by World Health Organization as of January 2019. The transmission of the virus was expected to be from the camels found in Middle Eastern countries via the animal and human interaction. The genome structure provided information about the pathogenicity and associated virulent factors present in the virus. Recent studies suggested that there were limited insight available on the development of novel therapeutic strategies to induce immunity against the virus. The severities of MERS-CoV infection highlight the necessity of effective approaches for the development of various therapeutic remedies. Thus, the present review comprehensively and critically illustrates the recent aspects on the epidemiology of the virus, the structural and functional features of the viral genome, viral entry and transmission, major mechanisms of pathogenesis and associated virulent factors, current animal models, detection methods and novel strategies for the development of vaccines against MERS-CoV. The review further illustrates the molecular and computational virtual screening platforms which provide insights for the identification of putative drug targets and novel lead molecules toward the development of therapeutic remedies.

Repurposing of chloroquine and some clinically approved antiviral drugs as effective therapeutics to prevent cellular entry and replication of coronavirus

“…From the various species of coronavirus, only six have been reported to cause disease in humans. These include HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) (Arabi et al, 2017;Skariyachan et al, 2019). SARS-CoV and MERS-CoV are beta coronaviruses, and are among the pathogens included in the World Health Organization's list of high-priority threats (Zumla et al, 2015).…”

The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose‐only exposure device

“…Nonhuman primate animal models of MERS-CoV in both rhesus macaques and common marmosets were established in previous reports, 6,7 however, these models are limited by restricted availability, high costs, expert husbandry requirements, and ethical concerns. 8,9 Traditional small animals such as mice, hamsters, and ferrets cannot be infected with MERS-CoV owing to absence of the necessary dipeptidyl peptidase 4 (DPP4) receptor that interacts with the receptor binding domain of the MERS-CoV spike protein (S protein) [10][11][12] MERS-CoV fails to replicate in mice, which are readily available, have a defined genetic background and low cost and are frequently used in infectious disease research, due to variations in the DPP4 receptor. Previous studies showed that transgenic mice expressing the human DPP4 (hDPP4) receptor could be infected intranasally with MERS-CoV and developed acute pneumonia.…”

First clinical trial of a MERS coronavirus DNA vaccine

“…No licensed MERS coronavirus vaccine is currently available, and substantial challenges exist to the development of such a vaccine. These include: (1) available animal models (eg, transduced mice, and transgenic mice, rabbits, rhesus macaques, marmosets, alpacas, and camels) might not mimic human disease; 7 (2) an immune correlate of protection has not been defined, and the protective immune response in natural infection is poorly understood, although both humoral and cellular responses are probably necessary for viral clearance; 8 (3) there is a theoretical risk of immune enhancement during MERS coronavirus infection after vaccination, possibly leading to immunopathological pulmonary eosinophilic infiltration; 9 (4) demonstration of efficacy in the field will probably not be possible, necessitating alternative regulatory pathways for licensure; and (5) if MERS shifts from a pattern of sporadic outbreaks to pandemic spread, it is not known whether vaccines based on current MERS coronavirus isolates will offer protection against pandemic strains.…”