**5. Discussion**

In the case of IPAC, it is common for microbicidal actives to be formulated into products intended for surface or hand hygiene. These products are used to interrupt the cycle of infection involving the indirect transfer of virus from contaminated fomites to the hand and then to mucous membranes of a susceptible individual. There is also the possibility of re-aerosolization of virus from a contaminated fomite [80–84], potentially leading to direct airborne transmission to mucous membranes of a susceptible person. As mentioned in the preceding sections, these routes of infection may be less important for those viruses that are primarily transmitted through insect vectors (e.g., Zika virus). Microbicides are typically used for all of the WHO Priority List viruses *as is* for disinfection of laboratory samples to render them safe for handling.

The stated purpose of this review was to identify gaps in the current state of the science regarding the virucidal efficacy of microbicides (including surface and hand hygiene agents) for viruses causing the current WHO Priority List diseases. The viruses that cause Priority List diseases are also mentioned in lists of pathogens of concern issued by other health agencies globally. For instance, Lassa virus, Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, Ebola virus, and Marburg virus are also mentioned in the National Institute of Allergy and Infectious Diseases (NIAID) Emerging Infectious Diseases/Pathogens priority A list [85]. The NIAID list was issued in 2018 and, therefore, did not include SARS-CoV-2. SARS-CoV-2 is certainly now a priority virus for NIAID [86]. A discussion of emerging and reemerging viruses can be found in Morens and Fauci [87]. Listed among other emerging viruses in that review are SARS-CoV, MERS-CoV, SARS-CoV-2, Zika virus, Rift Valley fever virus; Nipah virus, Hendra virus, Ebola virus, and Marburg virus. Additional viruses not mentioned in the WHO Priority List include additional bunyaviruses, influenza virus strains, enteroviruses and poxviruses [87]. A recent

review of emerging and re-emerging viral infections by Schwartz [88] also mentions, among other viruses, Lassa virus, Ebola virus, Marburg virus, Zika virus, SARS-CoV-2, MERS-CoV, and SARS-CoV, and Rift Valley fever virus. Knowledge gaps outlined in that review did not include gaps in information on disinfection/ surface hygiene and hand hygiene. The WHO also maintains what is referred to as an "R&D Blueprint" and an "R&D Roadmap" to provide guidance on appropriate responses to Priority List disease outbreaks and to develop ways to improve global responses to future epidemics [89]. This was last updated in 2017 and, therefore, is not as current as the WHO Priority List. The R&D Blueprint also is more a description of the types of knowledge gaps for epidemic preparedness (vaccine testing, diagnostic technologies, therapeutic interventions, vector control) than a list of viruses of concern [89].

It was assumed at the time of undertaking this literature review that, by definition, information would be minimal for at least some of the Priority List viruses (**Table 1**), and this indeed turned out to be the case. Although it is clear that knowledge for one member of a given virus family should be informative for other members of the same virus family, the purpose of this review was to identify knowledge gaps for the specific viruses of concern, not to review inactivation information for surrogate viruses from the same or other viruses from the families (**Table 1**). Such an exercise, while of value for IPAC of these specific viruses, was considered to be well beyond the scope of this chapter. Readers interested in identifying microbicides with efficacy for inactivating any of the Priority List viruses are encouraged to review the literature cited in this chapter, to consider the predictions of virucidal efficacy discussed in Section 3 of this chapter, and to search and review the literature for inactivation of other members of the virus family of interest.

It can be safely said that, following these steps, one may arrive at a list of microbicides and conditions (temperature, microbicide concentration, contact time, testing matrix, etc.) that should adequately inactivate each of the Priority List viruses. As an example, there are extremely limited data for the paramyxoviruses Nipah virus and other henipaviruses. There are, however, a variety of other paramyxoviruses for which inactivation data are available, and the lipid-disrupting agents and broad-spectrum microbicides effective against the less lethal paramyxoviruses (e.g., respiratory syncytial virus, parainfluenza virus type 3) should be equally effective against the Priority List paramyxoviruses.

It is clear that during the ongoing SARS-CoV-2 pandemic, the majority of the resources of the public health community were applied to research into one or more of the many different aspects of SARS-CoV-2 for IPAC. In fact, many laboratories have been conducting research exclusively on SARS-CoV-2 during the ongoing pandemic. Because of this, literature on all aspects of the virus and the disease, COVID-19, has appeared on a relatively continuous basis. The relatively great amount of empirical data collected to date on the virucidal efficacy of microbicides for SARS-CoV-2, SARS-CoV, and MERS-CoV (**Table 4**) reflects this emphasis. Of course, during a pandemic impacting 435 million confirmed cases globally and 5.9 million global deaths as of February 28, 2022 [90], this universal focus on the virus and the disease was, and remains, appropriate, particularly with the emergence of Delta, Omicron, and other variants [91, 92].

It is also clear from this review of the literature on the virucidal efficacy of microbicides for the WHO Priority List viruses that relatively limited information is available on some viruses, especially the paramyxoviruses Nipah virus and related henipaviruses and the bunyaviruses CCHFV and RVFV. Rift Valley fever virus and CCHFV are infectious agents considered as bioterrorism threats, due in part to the paucity of knowledge on measures for mitigating the transmission of the viruses and severity of the associated diseases [93, 94]. Reviews of focus areas and

knowledge gaps for CCHFV [93–95] mention tick (vector) surveillance and vector control agents, but does not discuss knowledge gaps around surface disinfection or hand hygiene. For the arboviruses (Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, Zika virus), the possibility of contamination of high-touch environmental surfaces with patient blood spills and other patient excretions/secretions needs to be considered and transmission risk mitigated through application of effective microbicides. Further research into this topic is, therefore, required. For surface virucidal studies, the impact of the matrix in which the challenge virus is suspended at time of drying on the carrier should always be evaluated. As shown in the Zika surface inactivation studies (**Table 6**), virus deposited in a blood matrix does not appear to be effectively inactivated by the microbicides peracetic acid and chlorine, compared to inactivation of virus dried in the absence of the blood load [55].

It is to be expected that, as the current pandemic wanes, research into the more lethal, albeit less common, viral diseases mentioned in this chapter will be encouraged and undertaken at the BSL-3 and BSL-4 laboratories capable of safely handling these viruses. For instance, further studies need to be carried out on the virucidal efficacy of commonly used microbicides (surface and hand hygiene agents) for Lassa virus and Nipah virus in surface and suspension inactivation studies. This information will provide additional confirmation of the expectation that microbicides capable of inactivating enveloped viruses, in general, should be effective for these Priority List viruses. Until such data are generated, the IPAC community will continue to be able to leverage virucidal efficacy data for other enveloped and non-enveloped viruses per the Emerging Viral Pathogen Guidance for Antimicrobial Pesticides from the U.S. EPA [4, 5] and the European tiered approach for virucidal efficacy testing [96].
