PubMed · 1463474
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1992-01-24. Dengue.. https://pubmed.ncbi.nlm.nih.gov/1463474/
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Dengue is the most common global problem in recent times, particularly in tropical and subtropical areas, yet antivirals for therapy or prophylaxis are lacking. Millions of people are affected by this dengue virus, but no proper medication is available yet to cure this disease. One polyprotein that is encoded by the DENV genome is converted into structural and non-structural proteins that are necessary for viral pathogenesis and replication. Among these, the non-structural protein complex NS2B-NS3 is essential for viral polyprotein processing, replication, and host innate immune response control. It acts as a trypsin-like serine protease. The NS2B/NS3 protease is a key enzyme involved in viral replication and serves as a major target for drug development against the dengue virus. The NS3 protease has a conserved catalytic triad (His-Asp-Ser), whereas NS2B serves as an essential cofactor that stabilizes the active conformation of the enzyme and aids in substrate recognition. By disrupting interferon signalling pathways, the NS2B-NS3 protease not only aids in viral replication but also makes immune evasion easier. The compound that inhibits the action of this enzyme could be pioneering in the antiviral drug discovery process. This article provides a comprehensive overview of the detailed structural information of the viral protease (NS2B/NS3) enzyme with the mechanistic role of this enzyme, and highlights various inhibitors related to the NS2B/NS3 protease. A more thorough comprehension of this protease could facilitate the logical development of potent antiviral medications to prevent dengue infection.
Increased incidence of dengue haemorrhagic fever has been observed in South East Asia. The etiology, clinical features and epidemiology of dengue virus infections are presented, with special emphasis on experience from Thailand. Reduction of sources, in terms of eliminating breeding sites for mosquitos, is the major approach in controlling dengue haemorrhagic fever, an approach which can succeed only through participation by the local community. The involvement of schools has proven to be successful in campaigns to reduce mosquito breeding sites in Thailand.
Hundreds of thousands of dengue cases are reported worldwide each year. Given the difficulty in obtaining full reporting, the actual number of human infections is probably much higher than the number reported. Dengue is usually a nonspecific febrile illness that resolves with supportive therapy but the clinical spectrum ranges from asymptomatic infection through severe hemorrhage and sudden fatal shock. The pathophysiology of the severe forms of dengue may be related to sequential infection with different serotypes, variations in virus virulence, interaction of the virus with environmental and host factors or a combination of these factors. Control of dengue at the present time is dependent on control of the principal vector mosquito, A. aegypti. Efforts to achieve such control are now focusing on community education and action towards eliminating this mosquito's breeding sites near human dwellings. Vaccine development continues, but at present the only way to avoid dengue in an area where it is endemic or epidemic is to use repellents and mosquito barriers. The movement of people to and from tropical areas makes dengue an important differential diagnosis in any patient with an acute illness and history of recent travel to tropical areas. Because of continued infestation of the southeastern United States with A. aegypti, indigenous transmission in the continental United States remains a public health concern.