Antiviral therapeutics for chikungunya virus
TL;DR: This review provides an overview of the granted patents including the current status of antiviral strategies targeting CHIKV, a reemerging human arthropod borne virus, which has become a serious health concern due to the unavailability of any antiviral therapy/vaccine.
Abstract: Introduction: Chikungunya virus (CHIKV), a reemerging human arthropod borne virus, can causes global epidemic outbreaks and has become a serious health concern due to the unavailability of any antiviral therapy/vaccine. Extensive research has been conducted to target different proteins from CHIKV to curtail the spread of virus.Areas covered: This review provides an overview of the granted patents including the current status of antiviral strategies targeting CHIKV.Expert opinion: Under the current scenario, potential molecules and different approaches have been utilized to suppress CHIKV infection. MV-CHIKV and VRC-CHKVLP059-00-VP vaccine candidates have successfully completed phase I clinical trials and ribavirin (inhibitor) has shown significant inhibition of CHIKV replication and could be the most promising candidates. The drug resistance and toxicity can be modulated by using the inhibitors/drugs in combination. Moreover, nanoparticle formulations can improve the efficacy and bioavailability of drugs.
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TL;DR: A substantial review of literature illuminating the host factors and molecular mechanisms involved in innate/adaptive responses to viral infection, hijacking of signalling pathways by viruses and the intracellular metabolic pathways required for viral replication is provided in this article.
26 citations
TL;DR: A review of emerging infectious diseases associated with reports of ocular manifestations and summarizes details pertinent to practicing eye specialists is presented in this paper, where emerging infectious disease should be considered in the differential diagnosis of Ocular inflammatory conditions in patients inhabiting or returning from endemic territories.
Abstract: Emerging infectious diseases (EIDs) are an increasing threat to public health on a global scale. In recent times, the most prominent outbreaks have constituted RNA viruses, spreading via droplets (COVID-19 and Influenza A H1N1), directly between humans (Ebola and Marburg), via arthropod vectors (Dengue, Zika, West Nile, Chikungunya, Crimean Congo) and zoonotically (Lassa fever, Nipah, Rift Valley fever, Hantaviruses). However, specific approved antiviral therapies and vaccine availability are scarce, and public health measures remain critical. Patients can present with a spectrum of ocular manifestations. Emerging infectious diseases should therefore be considered in the differential diagnosis of ocular inflammatory conditions in patients inhabiting or returning from endemic territories, and more general vigilance is advisable in the context of a global pandemic. Eye specialists are in a position to facilitate swift diagnosis, improve clinical outcomes, and contribute to wider public health efforts during outbreaks. This article reviews those emerging viral diseases associated with reports of ocular manifestations and summarizes details pertinent to practicing eye specialists.
15 citations
TL;DR: Quinoline and quinolone derivatives attain significance in area of research and treatment of various life-threatening epidemics such as SARS, Zika virus, Ebola virus, Dengue and COVID-19 (currently).
Abstract: Pandemics are large‐scale outbreaks of infectious disease that can greatly increase morbidity and mortality all the globe. Since past 1990 till twentieth century, these infectious diseases have been major threat all over the globe associated with poor hygiene and sanitation. In light of these epidemics, researches have gained enormous rise in the developing the potential therapeutic treatment. Thus, revolutionized antibiotics have led to the near eradication of such ailments. Around 50 million prescription of antibiotics written in US per year according to center for disease control and prevention (CDC) report. There is a wide range of antibiotics available which differ in their usage and their mechanism of action. Among these quinoline and quinolone class of antibiotics get attention as they show tremendous potential in fighting the epidemics. Quinoline and quinolone comprise of two rings along with substitutions at different positions which is synthetically obtained by structural modifications of quinine. Quinoline and quinolone antibiotics exhibit extensive activities approved by FDA in the treatment of the several ailments such as gastrointestinal infections, urinary tract infections, prostate inflammation, malaria, gonorrhea, skin infection, colorectal cancer, respiratory tract infections. These are active against both gram‐negative and gram‐positive bacteria. This basic core of quinoline and quinolone is vital due to its capability of targeting the pathogen causing disease and beneficial in treating the infectious disease. They inhibit the synthesis of nucleic acid of bacteria which results in the rupture of bacterial chromosome due to the interruption of enzymes such as DNA gyrase and topoisomerase IV. There are various quinoline and quinolone compounds that are synthetically derived by applying different synthesis approaches which show a wide range of pharmacological activities in several diseases. The most commonly used are fluoro, chloro, and hydroxychloro derivatives of quinoline and quinolone. These compounds are helpful in the treatment of numerous epidemics as a chief and combination therapy. These quinoline and quinolone pharmacophore fascinate the interest of researchers as they inhibit the entry of virus in host cell and cease its replication by blocking the host receptor glycosylation and proteolytic processing. They act as immune modulator by inhibiting autophagy and reduction of both lysosomal activity and production of cytokine. Therefore, quinoline and quinolone derivatives attain significance in area of research and treatment of various life‐threatening epidemics such as SARS, Zika virus, Ebola virus, dengue, and COVID‐19 (currently). In this chapter, the research and advancements of quinoline‐ and quinolone‐based antibiotics in epidemic management are briefly discussed.
12 citations
TL;DR: In this article, the authors summarize the current understanding of human and viral macrodomains that are related to mono-ADP-ribosylation, with emphasis on the search for inhibitors.
11 citations
TL;DR: In this paper , the anti-Chikungunya virus (CHIKV) has reemerged as a global public health threat, and a telmisartan (TM) was investigated for activity against CHIKV.
Abstract: Chikungunya virus (CHIKV) has reemerged as a global public health threat. The inflammatory pathways of the renin-angiotensin system (RAS) and peroxisome proliferator-activated receptor-gamma (PPAR-γ) are usually involved in viral infections. Thus, telmisartan (TM), which is known to block the angiotensin 1 (AT1) receptor and activate PPAR-γ, was investigated for activity against CHIKV. The anti-CHIKV effect of TM was investigated in vitro (Vero cells, RAW 264.7 cells, and human peripheral blood mononuclear cells [hPBMCs]) and in vivo (C57BL/6 mice). TM was found to abrogate CHIKV infection efficiently (50% inhibitory concentration (IC50) of 15.34 to 20.89 μM in the Vero cells and RAW 264.7 cells, respectively). Viral RNA and proteins were reduced remarkably. Additionally, TM interfered in the early and late stages of the CHIKV life cycle with efficacy during pretreatment and posttreatment. Moreover, the agonist of the AT1 receptor and an antagonist of PPAR-γ increased CHIKV infection, suggesting that the antiviral potential of TM occurs through modulating host factors. In addition, reduced activation of all major mitogen-activated protein kinases (MAPKs), NF-κB (p65), and cytokines by TM occurred through the inflammatory axis and supported the fact that the anti-CHIKV efficacy of TM is partly mediated through the AT1/PPAR-γ/MAPKs pathways. Interestingly, at a human equivalent dose, TM abrogated CHIKV infection and inflammation significantly, leading to reduced clinical scores and complete survival of C57BL/6 mice. Additionally, TM reduced infection in hPBMC-derived monocyte-macrophage populations in vitro. Hence, TM was found to reduce CHIKV infection by targeting both viral and host factors. Considering its safety and in vivo efficacy, it can be a suitable candidate in the future for repurposing against CHIKV.
10 citations
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TL;DR: This paper describes the new developments in PubChem, a key chemical information resource for the biomedical research community, which released new web interfaces, such as PubChem Target View page, Sources page, Bioactivity dyad pages and Patent View page.
Abstract: PubChem (https://pubchem.ncbi.nlm.nih.gov) is a key chemical information resource for the biomedical research community. Substantial improvements were made in the past few years. New data content was added, including spectral information, scientific articles mentioning chemicals, and information for food and agricultural chemicals. PubChem released new web interfaces, such as PubChem Target View page, Sources page, Bioactivity dyad pages and Patent View page. PubChem also released a major update to PubChem Widgets and introduced a new programmatic access interface, called PUG-View. This paper describes these new developments in PubChem.
2,083 citations
TL;DR: An update on chikungunya virus with regard to its epidemiology, molecular virology, virus-host interactions, immunological responses, animal models, and potential antiviral therapies and vaccines is provided.
Abstract: Re-emergence of chikungunya virus, a mosquito-transmitted pathogen, is of serious public health concern. In the past 15 years, after decades of infrequent, sporadic outbreaks, the virus has caused major epidemic outbreaks in Africa, Asia, the Indian Ocean, and more recently the Caribbean and the Americas. Chikungunya virus is mainly transmitted by Aedes aegypti mosquitoes in tropical and subtropical regions, but the potential exists for further spread because of genetic adaptation of the virus to Aedes albopictus, a species that thrives in temperate regions. Chikungunya virus represents a substantial health burden to affected populations, with symptoms that include severe joint and muscle pain, rashes, and fever, as well as prolonged periods of disability in some patients. The inflammatory response coincides with raised levels of immune mediators and infiltration of immune cells into infected joints and surrounding tissues. Animal models have provided insights into disease pathology and immune responses. Although host innate and adaptive responses have a role in viral clearance and protection, they can also contribute to virus-induced immune pathology. Understanding the mechanisms of host immune responses is essential for the development of treatments and vaccines. Inhibitory compounds targeting key inflammatory pathways, as well as attenuated virus vaccines, have shown some success in animal models, including an attenuated vaccine strain based on an isolate from La Reunion incorporating an internal ribosome entry sequence that prevents the virus from infecting mosquitoes and a vaccine based on virus-like particles expressing envelope proteins. However, immune correlates of protection, as well as the safety of prophylactic and therapeutic candidates, are important to consider for their application in chikungunya infections. In this Review, we provide an update on chikungunya virus with regard to its epidemiology, molecular virology, virus-host interactions, immunological responses, animal models, and potential antiviral therapies and vaccines.
289 citations
TL;DR: Administration of a single dose of a combination of two neutralizing MAbs limited the development of resistance and protected immunocompromised mice against disease when given 24 to 36 hours before CHIKV-induced death.
Abstract: Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes global epidemics of a debilitating polyarthritis in humans. As there is a pressing need for the development of therapeutic agents, we screened 230 new mouse anti-CHIKV monoclonal antibodies (MAbs) for their ability to inhibit infection of all three CHIKV genotypes. Four of 36 neutralizing MAbs (CHK-102, CHK-152, CHK-166, and CHK-263) provided complete protection against lethality as prophylaxis in highly susceptible immunocompromised mice lacking the type I IFN receptor (Ifnar−/−) and mapped to distinct epitopes on the E1 and E2 structural proteins. CHK-152, the most protective MAb, was humanized, shown to block viral fusion, and require Fc effector function for optimal activity in vivo. In post-exposure therapeutic trials, administration of a single dose of a combination of two neutralizing MAbs (CHK-102+CHK-152 or CHK-166+CHK-152) limited the development of resistance and protected immunocompromised mice against disease when given 24 to 36 hours before CHIKV-induced death. Selected pairs of highly neutralizing MAbs may be a promising treatment option for CHIKV in humans.
256 citations
TL;DR: The combination of IFN-alpha2b and ribavirin had a subsynergistic antiviral effect on these two alphaviruses and should be evaluated for the treatment of these infections.
239 citations
TL;DR: The chikungunya VLP vaccine was immunogenic, safe, and well tolerated, and represents an important step in vaccine development to combat this rapidly emerging pathogen.
214 citations