Dengue fever is a flu-like ailment propagated by female mosquitos of the Aedes aegypti species. It is also known as dandaka jwara in Ayurveda. It is most common in the world's subtropical and tropical climate zones. Vomiting, severe headache, nausea, rashes, joint pain, pain behind the eyes, muscle pain, and swollen glands are all common dengue symptoms. If not handled promptly, these symptoms can lead to more severe issues such as exhaustion, blood in the vomit, continuous vomiting, bleeding gums, restlessness, severe abdominal pain, and rapid bleeding. Because there is no specific medication for dengue fever, the disease is treated by eliminating and managing the symptoms. Fortunately, there are a variety of ayurvedic remedies (like Carica papaya L., Cissampelos pareira L., etc. ) that can help to tackle the same by strengthening the immune system and controlling hyperthermia. This review article provides a comprehensive overview of dengue virus infections, clinical symptoms, diagnosis, mitigation, and treatments, focusing on ayurvedic and herbal remedies. 

Ayurvedic and Other Herbal Remedies For Dengue: An Update

Aim: Considering the present alarming situation of COVID-19 pandemic, we concentrated on evaluating the efficacy of a novel natural antiviral drug-candidate andrographolide against SARS-CoV-2 through an in silico model of study. Materials & methods: Interaction of andrographolide against the major host molecules that are responsible for SARS-CoV-2 pathogenesis were determined using bio-computational tools, in other words, molecular docking, molecular dynamics simulation and pharmacodynamics–pharmacokinetics analysis. Result: Computational findings represent that andrographolide efficiently interacts with the major human–host-associated putative drug-targets of viral-entry points like furin (-10.54 kcal/mol), TMPRSS-2 (-9.50 kcal/mol), ACE2 (-8.99 kcal/mol) and Cathepsin L (-8.98 kcal/mol). Moreover, it also blocks the inflammatory regulators including TLR4-MD2 and IL-6, which promote virus-induced inflammation leading to cytokine storm in the host body. Conclusion: This work elucidates that, the candidature of andrographolide can be utilized as a potent natural agent for the therapeutic intervention of SARS-CoV-2 through host-directed treatment.

Andrographolide induces anti-SARS-CoV-2 response through host-directed mechanism: an in silico study

In accordance with the importance of telomerase inhibition as a potential target in cancer therapy, and increasing reports on the association between short telomeres and severe COVID-19 symptoms as well as extensive application of Andrographis paniculata as a remedy for both cancer and SARS-CoV-2, the present study aimed at investigating the impact of the plant's extracts on telomerase activity (as an important enzyme regulating telomere length). Telomerase inhibition in MCF-7 cells treated with the Dichloromethane, ethanol, water, and methanol extracts of A. paniculata was assessed using Telomerase Repeated Amplification Protocol (TRAP). The above-mentioned extracts inhibited telomerase by 80.3 ± 1.4%, 78.5 ± 1.35%, 77.5 ± 1.81%, and 73.7 ± 1.81%, respectively. Furthermore, the flow cytometry analysis showed that the water and methanol extracts induced higher rates of total apoptosis by 32.8% and 25%, respectively, compared with dichloromethane (10.07%) and ethanol (10.7%) extracts. The inhibitory effect of A. paniculata on telomerase activity can be considered as a potential immunity modulator in cancer therapy; however, telomerase inhibition as a safe approach to SARS-CoV-2 is arguable. Two mechanisms can be considered accordingly; (a) reducing the existing population of short telomeres via telomerase inhibition in cancer cells (arresting proliferation and finally cell death) may decrease the susceptibility against SARS-CoV-2, especially in cancer patients or patients prone to cancer, and (b) increasing the population of short telomeres via telomerase inhibition in normal/somatic cells may increase the susceptibility against SARS-CoV-2. Therefore, the telomerase inhibition of A. paniculata as an immunity modulator in cancer and COVID-19 should be investigated, carefully. 

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Andrographis paniculata extract as an immunity modulator against cancer via telomerase inhibition

Recent advances in natural products as potential inhibitors of dengue virus with a special emphasis on NS2b/NS3 protease.

Infection by Zika virus (ZIKV), a mosquito-transmitted arbovirus and a member of Flavivirus, could make pediatric microcephaly and Guillain-Barré syndrome, which remains an ongoing global threat. The efficient antivirals to ZIKV infection are of great medical need. Andrographolide and its analogues were discovered to be active against flaviviral infection. In this study, we discovered some dehydroandrographolide derivatives of 3-oximido- or 3-alcohol-19-hindered ether to be potent anti-ZIKV agents with low cytotoxicities (CC50 > 200 μM). Time of addition assay suggests that compound 5a and its analogues act on inhibition of post-entry stage of ZIKV life cycle. It is discovered by experimental and molecular docking studies that active anti-ZIKV compounds of 3a, 5a, 5b and 5c possess inhibitory activities of ZIKV NS5 MTase (methyl transferase) enzymatic activity. Preliminary SAR reveals that C19-modification with bulky groups is necessary for anti-ZIKV infection and replication, anti-ZIKV activity of 5a comes from itself bearing hindered trityl ether but not from its instability, the backbone of dehydroandrographolide is more effective against ZIKV infection than that of andrographolide, and 3-oxime derivatives are more active against ZIKV infection than 3-alcohol derivatives. To our knowledge, 5a is the first reported MTase inhibitor of andrographolide derivatives. More importantly, discovery of active compound 5b with acid-stable 19-OCHPh2 against ZIKV infection is valued and gives us a clue to design and discover generally acid-stable anti-ZIKV agents. 

Discovery of dehydroandrographolide derivatives with C19 hindered ether as potent anti-ZIKV agents with inhibitory activities to MTase of ZIKV NS5.

Andrographispaniculata (Burm.f.) Nees has been used as a traditional medicine in Asian countries, especially China, India, Vietnam, Malaysia, and Indonesia. This herbaceous plant extract contains active compounds with multiple biological activities against various diseases, including the flu, colds, fever, diabetes, hypertension, and cancer. Several isolated compounds from A. paniculata, such as andrographolide and its analogs, have attracted much interest for their potential treatment against several virus infections, including SARS-CoV-2. The mechanisms of action in inhibiting viral infections can be categorized into several types, including regulating the viral entry stage, gene replication, and the formation of mature functional proteins. The efficacy of andrographolide as an antiviral candidate was further investigated since the phytoconstituents of A. paniculata exhibit various physicochemical characteristics, including low solubility and low bioavailability. A discussion on the delivery systems of these active compounds could accelerate their development for commercial applications as antiviral drugs. This study critically reviewed the current antiviral development based on andrographolide and its derivative compounds, especially on their mechanism of action as antiviral drugs and drug delivery systems.

A’liyatur Rosyidah

Papers

Antiviral Activities of Andrographolide and Its Derivatives: Mechanism of Action and Delivery System.