The development of a vaccine against SARS-CoV-2 infection is on the way. To prepare for public availability, the acceptability of a hypothetical COVID-19 vaccine and willingness to pay (WTP) were a...

Background: Dengue is a major mosquito-borne disease currently with no effective antiviral or vaccine available. Effort to find antivirals for it has focused on bioflavonoids, a plant-derived polyphenolic compounds with many potential health benefits. In the present study, antiviral activity of four types of bioflavonoid against dengue virus type -2 (DENV-2) in Vero cell was evaluated. Anti-dengue activity of these compounds was determined at different stages of DENV-2 infection and replication cycle. DENV replication was measured by Foci Forming Unit Reduction Assay (FFURA) and quantitative RT-PCR. Selectivity Index value (SI) was determined as the ratio of cytotoxic concentration 50 (CC₅₀) to inhibitory concentration 50 (IC₅₀) for each compound. Results: The half maximal inhibitory concentration (IC₅₀) of quercetin against dengue virus was 35.7 μg mL^-1 when it was used after virus adsorption to the cells. The IC₅₀ decreased to 28.9 μg mL^-1 when the cells were treated continuously for 5 h before virus infection and up to 4 days post-infection. The SI values for quercetin were 7.07 and 8.74 μg mL^-1, respectively, the highest compared to all bioflavonoids studied. Naringin only exhibited anti-adsorption effects against DENV-2 with IC₅₀ = 168.2 μg mL^-1 and its related SI was 1.3. Daidzein showed a weak anti-dengue activity with IC₅₀ = 142.6 μg mL^-1 when the DENV-2 infected cells were treated after virus adsorption. The SI value for this compound was 1.03. Hesperetin did not exhibit any antiviral activity against DENV-2. The findings obtained from Foci Forming Unit Reduction Assay (FFURA) were corroborated by findings of the qRT-PCR assays. Quercetin and daidzein (50 μg mL^-1) reduced DENV-2 RNA levels by 67% and 25%, respectively. There was no significant inhibition of DENV-2 RNA levels with naringin and hesperetin. Conclusion: Results from the study suggest that only quercetin demonstrated significant anti-DENV-2 inhibitory activities. Other bioflavonoids, including daidzein, naringin and hesperetin showed minimal to no significant inhibition of DENV-2 virus replication. These findings, together with those previously reported suggest that select group of bioflavonoids including quercetin and fisetin, exhibited significant inhibitory activities against dengue virus. This group of flavonoids, flavonol, could be investigated further to discover the common mechanisms of inhibition of dengue virus replication.

Japanese encephalitis (JE), a mosquito-borne viral disease, is endemic to the entire east and southeast Asia, and some other parts of the world. Currently, there is no effective therapeutic available for JE; therefore, finding the effective antiviral agent against JEV replication is crucial. In the present study, the in vitro antiviral activity of baicalein and quercetin, two purportedly antiviral bioflavonoids, was evaluated against Japanese encephalitis virus (JEV) replication in Vero cells. Anti-JEV activities of these compounds were examined on different stages of JEV replication cycle. The effects of the compounds on virus replication were determined by foci forming unit reduction assay (FFURA) and quantitative RT-PCR. Baicalein showed potent antiviral activity with IC₅₀ = 14.28 µg/mL when it was introduced to the Vero cells after adsorption of JEV. Quercetin exhibited weak anti-JEV effects with IC₅₀ = 212.1 µg/mL when the JEV infected cells were treated with the compound after virus adsorption. However, baicalein exhibited significant effect against JEV adsorption with IC₅₀ = 7.27 µg/mL while quercetin did not show any anti-adsorption activity. Baicalein also exhibited direct extracellular virucidal activity on JEV with IC₅₀ = 3.44 µg/mL. However, results of quantitative RT-PCR experiments confirmed the findings from FFURA. This study demonstrated that baicalein should be considered as an appropriate candidate for further investigations, such as the study of molecular and cellular mechanism(s) of action and in vivo evaluation for the development of an effective antiviral compound against Japanese encephalitis virus.

Background: Dengue is a serious arboviral disease currently with no effective antiviral therapy or approved vaccine available. Therefore, finding the effective compound against dengue virus (DENV) replication is very important. Among the natural compounds, bioflavonoids derived mainly from plants are of interest because of their biological and medicinal benefits.Methods: In the present study, antiviral activity of a bioflavonoid, baicalein, was evaluated against different stages of dengue virus type 2 (DENV-2) replication in Vero cells using focus forming unit reduction assay and quantitative RT-PCR.Results: Baicalein inhibited DENV-2 replication in Vero cells with IC₅₀= 6.46 μg/mL and SI= 17.8 when added after adsorption to the cells. The IC₅₀against DENV-2 was 5.39 μg/mL and SI= 21.3 when cells were treated 5 hours before virus infection and continuously up to 4 days post infection. Baicalein exhibited direct virucidal effect against DENV-2 with IC₅₀= 1.55 μg/mL and showed anti-adsorption effect with IC₅₀= 7.14 μg/mL.Conclusions: Findings presented here suggest that baicalein exerts potent antiviral activity against DENV. Baicalein possesses direct virucidal activity against DENV besides its effects against dengue virus adsorption and intracellular replication of DENV-2. Baicalein, hence, should be considered forin vivoevaluation in the development of an effective antiviral compound against DENV.

Dengue is a mosquito-borne viral disease endemic in many countries in the tropics and sub-tropics. The disease affects mainly children, but in recent years it is becoming more of an adult disease. Malaysia experienced a large dengue outbreak in 2006 to 2007, involving mostly adults, with a high number of deaths. We undertook a retrospective study to examine dengue death cases in our hospital from June 2006 to October 2007 with a view to determine if there have been changes in the presentation of severe to fatal dengue. Nine of ten fatal cases involved adult females with a median age of 32 years. All had secondary dengue infection. The mean duration of illness prior to hospitalization was 4.7 days and deaths occurred at an average of 2.4 days post-admission. Gastrointestinal pain, vomiting, diarrhea, intravascular leakages and bleeding occurred in the majority of cases. DSS complicated with severe bleeding, multi-organ failure and coagulopathy were the primary causes of deaths. Seven patients presented with thrombocytopenia and hypoalbuminemia, five of which had hemoconcentration and increased ALT and AST indicative of liver damage. Co-morbidities particularly diabetes mellitus was common in our cohort. Prominent unusual presentations included acute renal failure, acute respiratory distress syndrome, myocarditis with pericarditis, and hemorrhages over the brain and heart. In our cohort, dengue fatalities are seen primarily in adult females with secondary dengue infection. The majority of the patients presented with common clinical and laboratory warning signs of severe dengue. Underlying co-morbidities may contribute to the rapid clinical deterioration in severe dengue. The uncommon presentations of dengue are likely a reflection of the changing demographics where adults are now more likely to contract dengue in dengue endemic regions. Dengue continues to be a major mosquito-borne disease of serious public health concern. Children are usually the most affected group, but in recent decades, dengue and severe dengue have become more common among adults. Here we reviewed ten fatal dengue cases with a view to determine if there have been changes in the presentation of severe to fatal dengue. Our findings revealed high dengue mortality among adult females, associated with secondary dengue infection. Underlying co-morbidities particularly diabetes mellitus were common in our cohort. This may contribute to the rapid deterioration of clinical condition seen in severe dengue. Most patients presented with common clinical and laboratory warning signs for severe dengue. Uncommon presentations seen among our fatal cases are likely a reflection of the changing demography of dengue from children to more of an adult disease in dengue endemic countries. Our findings, hence, emphasize the importance of healthcare awareness of clinical warning signs for severe dengue, especially in adult females with underlying co-morbidities and secondary dengue infection.

The ten member states of the Association of Southeast Asian Nations (ASEAN) constitute an economic powerhouse, yet these countries also harbor a mostly hidden burden of poverty and neglected tropical diseases (NTDs). Almost 200 million people live in extreme poverty in ASEAN countries, mostly in the low or lower middle-income countries of Indonesia, the Philippines, Myanmar, Viet Nam, and Cambodia, and many of them are affected by at least one NTD. However, NTDs are prevalent even among upper middle-income ASEAN countries such as Malaysia and Thailand, especially among the indigenous populations. The three major intestinal helminth infections are the most common NTDs; each helminthiasis is associated with approximately 100 million infections in the region. In addition, more than 10 million people suffer from either liver or intestinal fluke infections, as well as schistosomiasis and lymphatic filariasis (LF). Intestinal protozoan infections are widespread, while leishmaniasis has emerged in Thailand, and zoonotic malaria (Plasmodium knowlesi infection) causes severe morbidity in Malaysia. Melioidosis has emerged as an important bacterial NTD, as have selected rickettsial infections, and leptospirosis. Leprosy, yaws, and trachoma are still endemic in focal areas. Almost 70 million cases of dengue fever occur annually in ASEAN countries, such that this arboviral infection is now one of the most common and economically important NTDs in the region. A number of other arboviral and zoonotic viral infections have also emerged, including Japanese encephalitis; tick-borne viral infections; Nipah virus, a zoonosis present in fruit bats; and enterovirus 71 infection. There are urgent needs to expand surveillance activities in ASEAN countries, as well as to ensure mass drug administration is provided to populations at risk for intestinal helminth and fluke infections, LF, trachoma, and yaws. An ASEAN Network for Drugs, Diagnostics, Vaccines, and Traditional Medicines Innovation provides a policy framework for the development of new control and elimination tools. Together with prominent research institutions and universities, the World Health Organization (WHO), and its regional offices, these organizations could implement important public health improvements through NTD control and elimination in the coming decade.