Progress on the Prevention and Treatment of Hantavirus Disease

Abstract

Hantaviruses, members of the order Bunyavirales, family Hantaviridae, have a world-wide distribution and are responsible for greater than 150,000 cases of disease per year. The spectrum of disease associated with hantavirus infection include hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) also known as hantavirus cardiopulmonary syndrome (HCPS). There are currently no FDA-approved vaccines or treatments for these hantavirus diseases. This review provides a summary of the status of vaccine and antiviral treatment efforts including those tested in animal models or human clinical trials.

Vaccines and Therapeutics Against Hantaviruses

“…For new world hantaviruses, passive immunization with either patient-derived or vaccine-induced NAbs was capable of protecting against lethal ANDV challenge in hamsters (Manigold and Vial, 2014). A non-randomized multicenter trial using plasma from HCPS convalescent patients for the treatment of acute HCPS has been carried out in Chile, showing that plasma containing high titers of NAbs against ANDV could significantly reduce case fatality rate from 32 to HCPS and HFRS Mertz et al, 2004;Safronetz et al, 2011;Kobayashi et al, 2012;Chung et al, 2013;Ogg et al, 2013;Westover et al, 2016;Malinin and Platonov, 2017 Vial et al, 2013;Brocato and Hooper, 2019 Frontiers in Microbiology | www.frontiersin.org 14% (Vial et al, 2015). Considering the limited availability of convalescent plasma from HCPS survivors, goose polyclonal antibodies were acquired from ANDV DNA vaccine, and the purified IgY/IgY Fc from egg yolks could protect hamsters from lethal ANDV infection.…”

“…Another study also indicated that application of vandetanib, a tyrosine-kinase inhibitor preventing VEGFR2 phosphorylation, before ANDV infection could delay animal lethality and increase total survival by 23% in ANDV-challenged hamsters (Bird et al, 2016). In contrast, similar small molecules administered after the onset of viremia failed to protect hamsters from lethal ANDV challenge (Brocato and Hooper, 2019). Moreover, some other small molecules, such as angiopoietin 1 (Ang-1) and sphingosine 1-phosphate (S1P), were found to inhibit hantavirus-directed endothelial cell permeability in vitro (Gavrilovskaya et al, 2008), while further research in vivo should be performed to confirm their efficacy.…”

“…The immunomodulatory treatment of corticoids was firstly performed during the Korean war, but the case fatality rate was not improved (Sayer et al, 1955). In Chile, a retrospective analysis suggested that a high dose of methylprednisolone could reduce mortality in 22 HCPS patients (Brocato and Hooper, 2019). However, a double-blind clinical trial in Chile failed to observe a significantly improved outcome between methylprednisolone recipients and placebo recipients for HCPS.…”

“…Hantavirus is a virus transmitted mainly by rodent animals, mainly through urine, feces, and saliva and the aerosols produced by them, but rarely by the bites of infected animals (Brocato and Hooper, 2019). In recent years, the infection rate of hantavirus has increased in China and Europe (Dong et al, 2019).…”

5,6-Dichloro-2-Phenyl-Benzotriazoles: New Potent Inhibitors of Orthohantavirus

“…A few other candidates have been evaluated: Favipiravir, a pyrazine derivative endowed of anti-influenza properties and Vandetanib, a tyrosine-kinase inhibitor. The use of corticosteroids, unfortunately, does not determine benefit and immunotherapy although it has given encouraging results; in preventing and treating human hantavirus infections, it remains challenging [14].…”