PANVIPREP's priority virus list
Why did we select the five virus groups on PANVIPREP’s priority list?
PANVIPREP aims to develop antivirals active against an entire virus genus or family. Therefore, virus panels representing the genetic diversity within a particular virus group will be used to identify molecules with such broad(er)-spectrum activity. These can then be assumed to also inhibit the replication of any new virus from that group that may emerge in the future.
PANVIPREP will focus on five selected RNA virus families/genera: alphaviruses, coronaviruses, enteroviruses, flaviviruses, and the (related) paramyxo/pneumoviruses. These groups are prominently represented on the lists of high-priority viral diseases as compiled by WHO, CEPI, HERA, BMGF, NIAID and other organizations. They share (i) a demonstrated potential for zoonotic transfer and human infection, (ii) a high epidemic/pandemic potential and (iii) a limited availability or lack of appropriate countermeasures. Below, we list some of the major pathogens within the selected virus families/genera.
Alphaviruses (Togavirus family), e.g., chikungunya virus, Western, Eastern & Venezuelan encephalitis viruses, Mayaro virus, Ross River virus.
The mosquito-borne alphaviruses can cause systemic infections with serious consequences (such as long-lasting arthritis; Chikungunya) or central nervous system infections (as in the case of Venezuelan encephalitis virus). The Chikungunya outbreak in 2013-2014 in the Caribbean and Latin America showcased how rapidly alphaviruses may spread in an immunological naïve population in regions with mosquito vectors. Climate change rapidly expands these regions, including Southern Europe, where local chikungunya virus outbreaks have occurred.
Coronaviruses, e.g., SARS-CoV, SARS-CoV-2, MERS-CoV; Human Coronaviruses NL63, HKU1, OC43 and 229E.
Coronaviruses cause mostly respiratory infections. Newly emerging CoVs have reported case-fatality rates of up to 10% for SARS-coronavirus and 35% for MERS-coronavirus. COVID-19 paralysed the global community in 2020 and 2021. An enormous reservoir of poorly characterized coronavirus species is circulating in wildlife, with a well-documented track record of host switching. They constitute a serious threat of future (local or pandemic) outbreaks of new respiratory infections.
Enteroviruses (Picornavirus family), e.g., poliovirus, EV-68, EV-71, Coxsackie, rhino and echo viruses.
The highly prevalent and diverse enterovirus group causes various (often lethal) diseases, including febrile illness, hand-foot-and-mouth disease, encephalitis, and paralysis. Global public health concerns have developed in recent years due to epidemics of enteroviruses-A71 and -D68. Vaccines exist against poliovirus and enterovirus-A71. However, due to the very large number of serotypes and capsid diversity, it is not feasible to develop pan-enterovirus vaccines. Thus, there is an urgent need for pan-enterovirus antivirals. WHO also expects to need at least two different antiviral drugs for the poliovirus eradication endgame.
Flaviviruses, e.g., yellow fever virus, dengue virus, Zika virus, West-Nile virus, Japanese encephalitis virus.
Flaviviruses can cause both systemic and CNS infections (e.g., microcephaly in new-borns caused by Zika virus). Tens of thousands of lethal cases of dengue, yellow fever and Japanese encephalitis are recorded annually. Flaviviruses can be spread by a range of arthropods or unknown vectors. There is an efficacious yellow fever vaccine and dengue vaccination is emerging, but there are no approved anti-flavivirus drugs. Mosquito-transmitted flaviviruses can rapidly emerge and spread, as illustrated by the explosive 2014-2017 Zika virus outbreak in Latin America. The expansion of regions where mosquito vectors are endemic is a problem shared with alphavirus infections (see above).
Paramyxo/pneumoviruses, e.g., measles virus, respiratory syncytial virus, hPIV, hMPV, and Henipaviruses (Nipah, Hendra, Cedar viruses).
Paramyxo/pneumoviruses infections can manifest as acute respiratory syndromes or can cause encephalitis. A particular concern is the extremely high-risk for human health posed by the zoonotic henipaviruses, with a case fatality rate of >75%. The paramyxo/pneumovirus cluster has an extensive track record of transfer to human populations. Their airborne transmission can be extremely efficient (measles is the most contagious virus we know). Pan-paramyxovirus and certainly pan-henipavirus inhibitors are needed to curb outbreaks as soon as newly emerging family members would be detected.