Elucidation of the molecular biology of Crimean-Congo hemorrhagic fever including its intricate genome and the biology of infection is imperative for devising therapeutic approaches to the disease.
Introduction to Crimean-Congo Hemorrhagic Fever
Crimean-Congo hemorrhagic fever (CCHF) is a virulent disease caused by the CCHFV virus and is primarily contracted from hyalomma gnawing ticks. The presentation of the disease encompasses chills, fever, muscle pain, and sometimes abdominal pain which, in turn, can escalate to more severe symptoms and a mortality rate of over 30%. Sectors of Africa, the Middle East, and Eastern Europe all have observed casses due to the rising tick population. CCHF is endemic in all those parts.
Fig.1 Molecular biological analysis of Crimean-Congo hemorrhagic fever virus. (Hawman D. W., et al., 2023)
Vaccine Development for CCHF
- Whole CCHFV which was inactivated by chemical agents has been used in the production of inactivated vaccines through cloning in the cell line or the brains of suckling mice.
- On the other hand, subunit vaccines are directed at specific target inside the body such as nucleoprotein NP and Glycoprotein precursor GPC in order to stimulate production of immune response in them.
- Among candidate vaccines, nucleic-acid vaccines such as DNA and mRNA have also positioned themselves as strong candidates with respect to CCHF.
- CCHFV antigen vaccines using viral vectors such as attenuated or inactivated viruses utilize the modality of recombinant viruses for the delivery of CCHFV genes.
Therapeutics Development for CCHF
Ribavirin, a nucleoside analogue, has been administered in a clinical setting with little success. In preclinical studies newer antiviral favipiravir has shown a drastic reduction in viral load and increased survival rate for the animals. Furthermore, passive immunity against CCHFV targeting viral proteins has been assisted by monoclonal antibodies. Due to the strong inflammatory response of CCHF, drugs of modulating cytokine release and immunotherapy are being attempted.
Table 1 Therapeutics for Crimean-Congo Hemorrhagic Fever. (Hawman D. W., et al., 2023)
| Compound |
Class |
Target |
Preclinical efficacy |
Clinical efficacy |
Comments |
| Ribavirin |
Nucleoside analogue |
RdRP |
Controversial efficacy in rodent models |
Controversial efficacy in cases |
Poor efficacy; early therapeutic start needed; should be discontinued or used in combination therapy |
| Favipiravir |
Nucleoside analogue |
RdRP |
Efficacy in rodent and NHP models |
Limited data or benefit |
Late therapeutic start effective in rodent models; clinical trials are needed |
| 2'-Deoxy-2'-fluorocytidine |
Nucleoside analogue |
RdRP |
Not done |
No data |
More preclinical studies are needed |
| Molnupiravir |
Nucleoside analogue |
RdRP |
No efficacy in rodent models |
No data |
Unlikely to proceed |
| Plasma or antibodies from survivors |
Neutralizing or non-neutralizing |
Viral proteins |
Not done |
Limited data or benefit |
More preclinical and/or clinical studies are needed |
| Monoclonal antibodies |
Neutralizing or non-neutralizing |
Viral proteins |
Limited data in rodent models |
No data |
More preclinical and/or clinical studies are needed |
| Corticosteroids |
Anti-inflammatory |
Host response |
Not done |
Limited data or benefit |
More preclinical and/or clinical studies are needed |
Our Services
Specializing in delivering all-encompassing services for the advancement of vaccines and therapeutics targeting Crimean-Congo Hemorrhagic Fever, our focus is on harnessing state-of-the-art scientific research and technological innovations. Our goal is to improve the speed and quality of the research and development efforts of pharmaceutical organizations across the globe.
Disease Models
- Neonatal Mice
- STAT-1 Knockout Mice
- IFNAR Knockout Mice
- IFNAGR Knockout Mice
- Cynomolgus Macaques
- Tick-Transmission Models
- Humanized Mouse Models (NSG-SGM3)
Our company offers state-of-the-art preclinical research services aimed at advancing the understanding of CCHFV and facilitating the development of vaccines and therapeutics. If you are interested in our services, please feel free to contact us.
References
- Hawman, David W., and Heinz Feldmann. "Crimean–Congo haemorrhagic fever virus." Nature Reviews Microbiology 21.7 (2023): 463-477.
- Ozdarendeli, Aykut. "Crimean–Congo hemorrhagic fever virus: progress in vaccine development." Diagnostics 13.16 (2023): 2708.
All of our services and products are intended for preclinical research use
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