Experimental Antiviral Therapeutic Studies for Human Rhinovirus Infections

Abstract

Rhinovirus infection is common and usually causes mild, self-limiting upper respiratory tract symptoms. Rhinoviruses can cause exacerbation of chronic respiratory diseases, such as asthma or chronic obstructive pulmonary disease, leading to a significant burden of morbidity and mortality. There has been a great deal of progress in efforts to understand the immunological basis of rhinovirus infection. However, despite a number of in vitro and in vivo attempts, there have been no effective treatments developed. This review article summarises the up to date virological and immunological understanding of these infections. We discuss the challenges researchers face, and key solutions, in their work to investigate potential therapies including in vivo rhinovirus challenge studies. Finally, we explore past and present experimental therapeutic strategies employed in the treatment of rhinovirus infections and highlight promising areas of future work.

Understanding Rhinovirus Circulation and Impact on Illness

“…Development of antivirals against RV infections has been the aim of numerous studies (summarized in multiple recent reviews [72][73][74][75][76][77]). Amongst early antiviral strategies, virustargeting capsid-binding drugs (Pleconaril, Pirodavir, Vapendavir) showed efficacy on preventing virus entry [78,79], but posed issues of rapidly emerging drug resistance [80][81][82].…”

A Pandemic Lesson for Global Lung Diseases: Exacerbations Are Preventable

“…HRV infections are an obvious target for drug therapy, although major challenges have been recognized ( 115 ). Approaches used include ribavirin, capsid binding inhibitors, 3C protease inhibitors, NO enhancers, and mammalian cathelicidins LL-37, protegrin-1, and SMAP-29 (reviewed in Reference 115 ).…”

“…HRV infections are an obvious target for drug therapy, although major challenges have been recognized ( 115 ). Approaches used include ribavirin, capsid binding inhibitors, 3C protease inhibitors, NO enhancers, and mammalian cathelicidins LL-37, protegrin-1, and SMAP-29 (reviewed in Reference 115 ). Molnupiravir, a novel antiviral recently identified as efficacious against SARS-CoV-2 ( 116 ), is a prodrug for the ribonucleoside analog β-D-N4-hydroxycytidine, which has broad-spectrum antiviral activity against RNA viruses, including influenza ( 117 ).…”

Anno 2021: Which antivirals for the coming decade?

“…Numerous active small molecules have been discovered through extensive in vitro screening campaigns that fall mainly into two mechanistic classes, i.e., capsid and 3C protease (3C pro ) inhibitors, with the former being the most advanced avenue for rhinovirus treatment. 92 , 93 However, lead compounds were either not developed or failed to meet the clinical criteria for their successful use because of their toxicity, poor pharmacology, or rapid resistance development [e.g., pleconaril, pirodavir, vapendavir, and rupintrivir). Moreover, a major challenge will be identifying anti-HRV compounds with a broad activity spectrum due to the circulation of approximately 160 different viral serotypes characterized by high mutation rates.…”