Since 2015, Zika Virus (ZIKV) has caused several outbreaks, with more than one million estimated cases occurring in North and South America. Pregnant women infected with ZIKV can transmit it to their unborn child, which can lead to miscarriage and microcephaly, a condition in which the baby’s head is much smaller than expected standard size.  Currently, there are no approved treatments available to address the public health impact of this disease. Previous studies have shown that favipiravir and ribavirin can inhibit ZIKV replication in vitro and provide protection against disease in some animal models.  In particular, favipiravir has been shown to be effective against several RNA viruses in different animal models of infection.  In this study, researchers conducted a study to assess the effectiveness of favipiravir and ribavirin in a mouse model of ZIKV infection.

When comparing favipiravir, ribarvirin, and a combination of the two to protect mice against lethal ZIKV challenge, researchers discovered that only favipiravir was effective against ZIKV infection. Protection from lethality with favipiravir was significantly different between male and female mice, with survival rates at 25% and 87%, respectively. These findings suggest that sex may be a variable in the efficacy of favipiravir against ZIKV and underscores the importance of using animal models of both sexes in preclinical models for medical countermeasures.  Further studies are required to define the underlying mechanisms of the sex differences associated with favipiravir treatment, as well as if it is a viable option as an intervention for other similar viral infections.

Reference: Matz et al. Favipiravir (T-705) Protects IFNAR−/− Mice against Lethal Zika Virus Infection in a Sex-Dependent Manner, Microorganisms, 9(6), 1178.

SAVE: NIAID’s 'Avengers-Like' Research Program for Evolving Pathogens

When the next SARS-CoV-2 variant of concern emerges in the world, NIAID will call on SAVE – its version of The Avengers – to quickly react and protect people. SAVE – which stands for SARS-CoV-2 Assessment of Viral Evolution– members assess whether mutations in variants can affect virus transmission, severity and immunity; test vaccines and therapeutics; and guide responses.

Like the comic book heroes fighting various mutant threats, SAVE focuses on mutations in SARS-CoV-2 and emerging virus variants. But program members say the global collaborative concept is a broad model for rapidly responding to evolving pathogens with pandemic potential.

NIAID assembled and coordinated SAVE scientists in January 2021, drawing on experts from around the world who specialize in relevant research fields such as viruses, the immune system, vaccines, epidemiology, structural biology, bioinformatics, virus genetics, and evolution.

SAVE members represent 58 different research sites located in the United States and around the world. Members participate within three sub-groups based on their expertise:

• Early Detection and Analysis
• In Vitro – what they can learn using flasks, beakers and tubes
• In Vivo – what they can learn in animal models that mimic human disease

“Collaboration within and across these groups has accelerated research and discovery due to immediate and open sharing of ideas, reagents, protocols and data,” 129 SAVE members said in a program overview just published in Nature.

SAVE emerged from the U.S. Department of Health and Human Services’ SARS-CoV-2 Interagency Group (SIG). The repeated emergence of COVID-19-causing variants of concern made SIG leaders recognize a critical need for scientists to rapidly generate, share and assess variant data in a highly coordinated manner to enable decision-making for public health.

The most telling example is how SAVE responded when the Omicron variant emerged in fall 2021. The group rapidly generated virus plasmids and spike protein; isolated, propagated and distributed authentic Omicron virus for research; submitted reagents to public repositories; performed binding and neutralization tests; and evaluated virus infection in different animal models.

Researchers then shared data from these studies with government agencies and submitted them as manuscripts online prior to peer-review – something rarely done before the COVID-19 pandemic. “The head-to-head comparison, review and discussion of unpublished data has yielded real-time peer review that would otherwise take months to achieve,” their summary states.

Each of the three groups has had to face various challenges in prioritizing work. For example:

• How much data is needed to provide relevant results in a desired, rapid timeframe? How can analysis be adjusted to account for low levels of sequencing in some countries and high levels in others?
• How can immune responses be enhanced to contribute to protection from infection and severe disease, and increase durability of immunity?
• Which animal models are best to evaluate protective immunity against a variant? Does immunity to variants differ in those who were infected after being vaccinated and those reinfected after having infection-induced immunity?

Regardless of challenges, the SAVE group sees a great need and opportunity for its type of collaboration in responding to outbreaks beyond the current pandemic.

“Over the past two decades, we have witnessed the emergence\re-emergence of several RNA viruses, including West Nile virus, H1N1 influenza virus, chikungunya virus, Zika virus, SARS-CoV-1, MERS-CoV, and Ebola virus, that have threatened global public health,” their summary states. “Developing collaborative programs between academic, industry and commercial partners is essential to respond to rapidly evolving viruses.”

Reference: M DeGrace, et al. Defining the risk of SARS-CoV-2 variants on immune protection. Nature DOI: 10.1038/s41586-022-04690-5 (2022).

January 30, 2022, marks the third World Neglected Tropical Diseases (NTDs) Day, presenting an opportunity to reflect both on the continuing burden imposed by these diseases and the significant progress made to curtail them. NTDs comprise viral, bacterial, fungal and parasitic diseases that, despite their various causes, have in common their substantial health, social and economic impacts, especially on marginalized populations living in tropical and subtropical countries.

Despite substantial progress in controlling NTDs in the past decade, these conditions still affect more than 1 billion people worldwide (WHO NTD Roadmap 2021-2030). Although NTDs do not typically cause death, they impede affected individuals’ ability to lead healthy lives, and reduce their growth and development, educational attainment and economic productivity. They also result in stigmatization and social inequities.   Consequently, NTDs contribute to a self-perpetuating cycle of illness leading to decreased human, social and economic development, which in turn fosters persistence of NTDs.

To break the cycle, new and improved interventions as well as effective implementation are needed. As part of its efforts to address global health, NIAID has long supported research and development to better understand, diagnose, treat and prevent NTDs. 

In these video interviews, NIAID staff highlight activities and advances that the Institute has supported as part of its collaborative work with partners around the world aimed at lifting the burden of NTDs.