Health-related quality of life and associated factors among COVID-19 individuals managed with indian traditional medicine: A cross-sectional study from south India.

Introduction: Coronavirus disease-2019 (COVID-19) had a multidimensional impact on human life. It affects the health-related quality of life (HRQoL) which is a perceived measure of physical and mental health. We estimated the EuroQol utility value for COVID-19 and the associated factors for those managed at Siddha COVID care centres in Tamil Nadu. Methods: A cross-sectional study was conducted by a telephonic interview of 2000 randomly selected COVID-19 adults tested positive during June 2020 to Jan 2021. We collected sociodemographic, clinical and EQ-5D-5L profile. Mean EQ-5D-5L summary utility values and EQ-VAS scores were estimated. Multivariate regression was used to examine the factors associated with EQ-5D-5L. Study protocol was approved by the Institutional ethics committee of Government Siddha Medical College, Chennai (GSMC-CH-3401/ME-2/050/2021). The committee waived the written informed consent considering the pandemic situation of emerging infectious diseases. Results: We interviewed 1047 participants. Of the total 68% were males with the median age (IQR) of 38 (29-51) years. The mean EQ-5D-5L utility score and EQ-VAS scores are 0.98 ± 0.05 and 92.14 ± 0.39 respectively. COVID-19 asymptomatic group reported a mean utility score of 0.99 ± 0.03 which is relatively more than the symptomatic group (0.97 ± 0.06),. EQ-VAS score was also reported high among the asymptomatic (95.45 ± 5.95) than the symptomatic (91.40 ± 8.69COVID-19. Conclusion: The severity of illness and the comorbidity are significantly associated with a low HRQoL of COVID-19 patients.

In Silico computational screening of Kabasura Kudineer - Official Siddha Formulation and JACOM against SARS-CoV-2 spike protein

Background: Siddha Medicine is a valuable therapeutic choice which is classically used for treating viral respiratory infections, this principle of medicine is proven to contain antiviral compounds. Objective: The study is aimed to execute the In Silico computational studies of phytoconstituents of Siddha official formulation Kabasura Kudineer and novel herbal preparation JACOM which are commonly used in treating viral fever and respiratory infectious diseases and could be affective against the ongoing pandemic novel corona virus disease SARS-CoV-2. Method: Cresset Flare software was used for molecular docking studies against the spike protein SARSCoV-2 (PDB ID: 6VSB). Further, we also conducted in silico prediction studies on the pharmacokinetics (ADME) properties and the safety profile in order to identify the best drug candidates by using online pkCSM and SwissADME web servers. Results: Totally 37 compounds were screened, of these 9 compounds showed high binding affinity against SARS-CoV-2 spike protein. All the phytoconstituents were free from carcinogenic and tumorigenic properties. Based on these, we proposed the new formulation called as "SNACKeV" Conclusion: Based on further experiments and clinical trials, these formulations could be used for effective treatment of COVID-19. (c) 2020 The Authors. Published by Elsevier B.V. on behalf of Institute of Transdisciplinary Health Sciences and Technology and World Ayurveda Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Safety and efficacy of a Siddha Medicine fixed regimen for the treatment of asymptomatic and mild COVID-19 patients.

Background: The Coronavirus disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a massive threat to public health worldwide. Siddha system of medicine is one of the traditional medicines of South India. The recommended formulations in Siddha Sasthric Medicines- Fixed Regimen (SSM-FiRe) are Amukkura tablets, Kaba Sura Kudineer (KSK) for asymptomatic COVID-19 positive (RT-PCR) patients, and Athimathuram tablets, Adathodai Manappagu syrup, Thippili Rasayanam, Brahmananda Bairavam tablet, and Notchi Kudineer for mild symptomatic patients. The core objective of the trial was to document the efficacy of SSM-FiRe in the prevention of asymptomatic and mild COVID-19 disease progression to the next level of severity, reduce the severity of symptoms and revert to RT-PCR Negative. Methods: An exploratory, prospective, open-labeled, single-arm, non-randomized trial was designed as per GCP guidelines to assess the efficacy of SSM-FiRe. Sixty RT-PCR positive participants who were asymptomatic or with mild COVID-19 symptoms were recruited for the study at the Siddha COVID Care Centre, Vyasarpadi, Chennai from June to August 2020. Nasal and oropharyngeal swab tests were performed on the 0, 7th, and 14th days. All participants were treated with SSM - FiRe regimen. All the participants were also assessed based on Siddha Yakkkaiyin Ilakkanam, which included Clinical symptoms and vitals. Laboratory investigations such as Haemogram, Liver Function Test, Renal Function Test, HbA1C, Electrolytes, Inflammatory markers, Cardiac profile, Immunoglobulins, and anti-SARS-CoV-2 antibody tests were performed. Results: 83% of COVID-19 patients turned RT-PCR negative on the 7th day and in most of the cases, symptoms were reduced within the first 5 days of admission. The RT-PCR cycle threshold (ct) value increased significantly (<0.001) after treatment and all the participants were RT-PCR negative, except one, who was positive even after 14 days. Anti-SARS-CoV-2 antibodies developed significantly (p-value - 0.006). LFT, RFT, CBC, Total proteins, and electrolytes continued to be in the normal range after treatment, indicating the safety of the intervention. Conclusion: Asymptomatic and mild COVID-19 disease can be well managed by SSM - FiRe treatment, Further studies could be taken up to strengthen the findings.

Understanding the activating mechanism of the immune system against COVID-19 by Traditional Indian Medicine: Network pharmacology approach.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmissions are occurring rapidly; it is raising the alarm around the globe. Though vaccines are currently available, the evolution and mutations in the SARS-CoV-2 threaten available vaccines' significance. The drugs are still undergoing clinical trials, and certain medications are approved for "emergency use" or as an "off-label" drug during the pandemic. These drugs have been effective yet accommodating side effects, which also can be lethal. Complementary and alternative medicine is highly demanded since it embraces a holistic approach. Since ancient times, natural products have been used as drugs to treat various diseases in the medical field and are still widely practiced. Medicinal plants contain many active compounds that serve as the key to an effective drug design. The Kabasura kudineer and Nilavembu kudineer are the two most widely approved formulations to treat COVID-19. However, the mechanism of these formulations is not well known. The proposed study used a network pharmacology approach to understand the immune-boosting mechanism by the Kabasura kudineer, Nilavembu kudineer, and JACOM in treating COVID-19. The plants and phytochemical chemical compounds in the Kabasura kudineer, Nilavembu kudineer, and JACOM were obtained from the literature. The Swiss target prediction algorithm was used to predict the targets for these phytochemical compounds. The common genes for the COVID-19 infection and the drug targets were identified. The gene-gene interaction network was constructed to understand the interactions between these common genes and enrichment analyses to determine the biological process, molecular functions, cellular functions, pathways involved, etc. Finally, virtual screening and molecular docking studies were performed to identify the most potential targets and significant phytochemical compounds to treat the COVID-19. The present study identified potential targets as ACE, Cathepsin L, Cathepsin B, Cathepsin K, DPP4, EGFR, HDAC2, IL6, RIPK1, and VEGFA. Similarly, betulinic acid, 5″-(2⁗-Hydroxybenzyl) uvarinol, antofine, (S)-1'-methyloctyl caffeate, (Z)-3-phenyl-2-propenal, 7-oxo-10α-cucurbitadienol, and PLX-4720 collectively to be potential treatment agents for COVID-19.

Siddha Medicine and Computer Modeling: A Treasure for SARS-CoV-2 Treatment

The SARS-CoV-2 was identified in December 2019 and spread quickly around the globe. Around 218 countries with 61,468,916 cases have been diagnosed as of November 27, 2020. The epidemic quarantine and symptomatic care plan control are the first step of the treatment in the absence of medicines and vaccines. The need for treatments/therapeutics is in high demand. Pharma companies are working around the clock to develop these treatments/therapeutics. Several traditional medicines are also followed as the treatments/therapeutics across the globe. In India, the traditional medicine system ranks to be one of the topmost promising treatments/therapeutics for ages. In COVID-19, the medicinal products for treatment, prophylaxis, and convalescence were listed based on the Siddha Medicine advisory provided by the Ministry of AYUSH. These drugs are recommended for the treatment and prophylaxis of symptoms. In reality, however, these medications have been in vogue for infectious diseases like Dengue and Chikungunya for the past two decades. In parallel, the in silico studies are positively helping in the drug discovery and unravel the drug mechanisms. The computational protein modeling techniques also play a significant role in identifying all the reference genome's proteins. This chapter discussed Siddha and Quarantine's traditional insight in viral diseases, Virus-based drug repurposing for coronaviruses, and various treatment, including significant drug repurposing and BSAA combination therapy. We have also used computational modeling techniques to identify and model the individual protein structures from the whole genome of SARS CoV-2. Finally, this chapter will explain the steps taken to develop and repurpose Kabasura Kudineer as a drug to inhibit the COVID-19 pandemic. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Kabasura Kudineer (KSK), a poly-herbal Siddha medicine, reduced SARS-CoV-2 viral load in asymptomatic COVID-19 individuals as compared to vitamin C and zinc supplementation: findings from a prospective, exploratory, open-labeled, comparative, randomized controlled trial, Tamil Nadu, India.

INTRODUCTION: Despite several ongoing efforts in biomedicine and traditional medicine, there are no drugs or vaccines for coronavirus disease 2019 (COVID-19) as of May 2020; Kabasura Kudineer (KSK), a polyherbal formulation from India's Siddha system of medicine, has been traditionally used for clinical presentations similar to that of COVID-19. We explored the efficacy of KSK in reducing viral load and preventing the disease progression in asymptomatic, COVID-19 cases. METHODS: A prospective, single-center, open-labeled, randomized, controlled trial was conducted in a COVID Care Centre in Chennai, India. We recruited reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 of 18 to 55 years of age, without clinical symptoms and co-morbidities. They were randomized (1:1 ratio) to KSK (60 mL twice daily for 7 days) or standard of care (7 days supplementation of vitamin C 60,000 IU morning daily and zinc 100 mg evening daily) groups. The primary outcomes were reduction in the SARS-CoV-2 load [as measured by cyclic threshold (CT) value of RT-PCR], prevention of progression of asymptomatic to symptomatic state, and changes in the immunity markers including interleukins (IL-6, IL-10, IL-2), interferon gamma (IFNγ), and tumor necrosis factor (TNF α). Siddha clinical assessment and the occurrence of adverse effects were documented as secondary outcomes. Paired t-test was used in statistical analysis. RESULTS: Viral load in terms of the CT value (RdRp: 95% CI = 1.89 to 5.74) declined significantly on the seventh day in the KSK group and that of the control group, more pronounced in the study group. None progressed to the symptomatic state. There was no significant difference in the biochemical parameters. We did not observe any changes in the Siddha-based clinical examination and adverse events in both groups. CONCLUSION: KSK significantly reduced SARS-CoV-2 viral load among asymptomatic COVID-19 cases and did not record any adverse effect, indicating the use of KSK in the strategy against COVID-19. Larger, multi-centric trials can strengthen the current findings. TRIAL REGISTRATION: Clinical Trial Registry of India CTRI2020/05/025215 . Registered on 16 May 2020.

In vitro Antiviral Activity of Kabasura Kudineer - Siddha Polyherbal Formulation Against Novel Coronavirus (SARS-CoV-2) (preprint)

Kabasura Kudineer (KSK) is a Sastric Siddha polyherbal formulation that has been used to treat the fever with influenza-like indication. The purpose of this study is to validate the antiviral activity of KSK against the novel SARS-CoV-2 virus. The antiviral activity of KSK against SARS-CoV-2 was assessed in Vero E6 cells and followed by an RT-PCR assay. KSK significantly inhibited SARS-CoV-2 replication in Vero E6 cells. These data indicate that KSK prevents the attack of its virus, rendering the use of these a novel COVID-19 infectious diseases strategy.

The psychological health status of nurses during the covid-19 outbreak: A cross-sectional survey study in Tamilnadu, India

Background: The COVID-19 pandemic, its rapid spread has impacted health care workers psychologically. Nurses experience heightened sense of anxiety as they are directly engaged in patient care. This study was designed to assess the Knowledge, attitude, fears of practicing nurses towards the Pandemic situation. Materials: The online questionnaire based descriptive study was conducted among nurses in the southern parts of Tamil Nadu. The Questionnaire was constructed by authors based on previous studies. The data collected were analyzed for descriptive statistics using SPSS 25. Results: A total of 186 completed questionnaires were analyzed for statistics. Female nurses were 146 (78.5%) whereas male participants were 40 (21.5%). Those with 5-10 years’ work experience had participated in large numbers (76). About 53% of the participants are working in Government hospitals. 93(50%) nurses had completed bachelor’s degree in nursing. About 108 nurses (58.1%) are from urban areas. The Mean knowledge score of the participants were 9.34. A majority of 144 nurses (77.4%) had scored more than 80% bloom cut-off marks. About 83 nurses had shown positive attitude in this COVID pandemic situation while more than half of the nurses agreed that spread among them can be controlled by regular Hospital infection control programs. In this study, about 111 nurses (59%) scored higher in anxiety/fear related questions showing that they are under occupation-related stress and anxiety. Conclusion: the study shows that the nurses are well informed about the COVID-19, its transmission and nature of spread. The fear/anxiety stress that most of the participants shows the imminent need for reinforcing active participation in counselling sessions, and hospital infection control programs to tackle the burden of work-related anxiety.

Antioxidative potential of kabasura kudineer (KSK), an official siddha polyherbal formulation

Siddha’s folk medicine system is used to enhance immune responses as preventive medicine. Siddha medicine’s enormousplethora of data will enhance human wellbeing. Since the oldyears, Kabasura Kudineer(KSK) has beenanimmunedrugtoseveralillnesses. Aqueous extract was employed for preparing the extract and analyzed for Total Antioxidant Capacity, Fe2+ chelating activity assay, Hydrogen peroxide scavenging activity, ABTS Scavenging assay and Reducing power assay. Thiswas found to possess high antioxidant properties of aqueous extract of KSK and their derivatives have been confirmed with the different tests. This experimentation further affirms the antioxidative nature of KSK extract, which further aid in the fight in this COVID-19 pandemic situation.

Pharmacological actions of contents of kabasura kudineer-a siddha formulation for fever with respiratory illness

Siddha system of medicine is a distinct therapeutic science with many single drugs and compound formulations used for treating a broad spectrum of ailments. Siddha categorizes the fever manifested by viral infestation into 64 types and it has developed medicines for each type. Kapacurak / Kabasurak Kutinir (KK) described in the Citta Vaittiyattirattu is the best promising polyherbal formulation of plant origin for curing viral infections especially with flu-like symptoms. As per Siddha system of medicine Kapacuram is defined as a fever with upper and lower respiratory catarrh. KK is one of the medicines advised for prevention of Coronavirus (COVID-19) outbreak in India by Ministry of AYUSH, Govt. of India. KK also emerged to be a popular traditional medicine for swine flu as well. The current review recapitulates active phytochemicals of all the 15 herbal drug ingredients in KK with the aim to provide it support for usage in flu-like viral infections spreading over the world in the scenario of having no modern medicines. Interestingly, out of 15 herbal ingredients in KK, Zingiber officinale rhizome, Andrographis paniculata whole plant, Syzygium aromaticum flower bud, Cyperus rotundus tuber, Sida acuta roots and Saussurea costus root have been proved to exhibit antiviral activities. All the ingredients have been proved to possess antinflammatory activities. Three proved to have antipyretic potential and five each proved to possess analgesic and immunomodulatory activities. There are ingredients with antiasthmatic and antispasmodic supporting its use in respiratory illnesses such as that caused by COVID-19. The study supports the usage of KK as a traditional Siddha medicine against respiratory illnesses with flu-like symptoms characteristic of SARS-CoV-2. © 2021, Association of Pharmaceutical Teachers of India. All rights reserved.

In Silico Docking Analysis of Poly Herbal Formulation Aadathodai Kudineer used in Siddha medicine in inhibiting Main Protease and ACE2 Receptor Spike protein SARS-CoV-2

Corona virus disease (COVID-19) is an infectious pandemic disease caused by the newly discovered novel corona virus. World Health Organization has declared the global health emergency due to COVID19 outbreak. Currently, there is no specific treatment or vaccine for fighting against this infectious disease. Aadathodai Kudineer is a drug indicated for Iya Erumal, Kozhai Kattu, Kabasuram. Upon the mortality and severity of the disease COVID19, we tried to identify the possible inhibition of phytocomponents of Aadathodai Kudineer in inhibiting Main Protease and ACE2 Receptor Spike protein SARS-CoV-2 through molecular docking studies. Methodology: In Silico molecular docking analysis was performed for phytocomponents present in the Aadathodai Kudineer formulation for targets main protease and ACE2 Receptor Spike protein, PDB ID: 6LU7 and PDB ID: 2AJF using Autodock tool. ADME properties was also predicted for all the above compounds. Results: Among the 9 active Phytocompounds present in the Aadathodai Kudineer formulation, Lupeol showed high binding affinity with COVID19 main protease and ACE2 receptor which shows the promising contrivance of protease inhibition. The ADME suggested that the formulation is free from toxic. Conclusion: The phytocomponents showed possible affinity towards these targets and has the lead molecules that inhibits COVID19 main protease and ACE2 receptor.

The efficacy of Siddha Medicine, Kabasura Kudineer (KSK) compared to Vitamin C & Zinc (CZ) supplementation in the management of asymptomatic COVID-19 cases: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The primary objectives of this study are to determine efficacy of Siddha medicine, Kabasura kudineer in reduction of SARS-CoV-2 viral load and reducing the onset of symptoms in asymptomatic COVID-19 when compared to Vitamin C and Zinc (CZ) supplementation. In addition, the trial will examine the changes in the immunological markers of the Siddha medicine against control. The secondary objectives of the trial are to evaluate the safety of the Siddha medicine and to document clinical profile of asymptomatic COVID-19 as per principles of Siddha system of Medicine. TRIAL DESIGN: A single centre, open-label, parallel group (1:1 allocation ratio), exploratory randomized controlled trial. PARTICIPANTS: Cases admitted at non-hospital settings designated as COVID Care Centre and managed by the State Government Stanley Medical College, Chennai, Tamil Nadu, India will be recruited. Eligible participants will be those tested positive for COVID-19 by Reverse Transcriptase Polymerase Chain reaction (RT-PCR) aged 18 to 55 years without any symptoms and co-morbidities like diabetes mellitus, hypertension and bronchial asthma. Those pregnant or lactating, with severe respiratory disease, already participating in COVID trials and with severe illness like malignancy will be excluded. INTERVENTION AND COMPARATOR: Adopting traditional methods, decoction of Kabasura kudineer will be prepared by boiling 5g of KSK powder in 240 ml water and reduced to one-fourth (60ml) and filtered. The KSK group will receive a dose of 60ml decoction, orally in the morning and evening after food for 14 days. The control group will receive Vitamin C (60000 IU) and Zinc tablets (100mg) orally in the morning and evening respectively for 14 days. MAIN OUTCOMES: The primary outcomes are the reduction in the SARS-CoV-2 load [as measured by cyclic threshold (CT) value of RT-PCR] from the baseline to that of seventh day of the treatment, prevention of progression of asymptomatic to symptomatic state (clinical symptoms like fever, cough and breathlessness) and changes in the immunity markers [Interleukins (IL) 6, IL10, IL2, Interferon gamma (IFNγ) and Tumor Necrosis Factor (TNF) alpha]. Clinical assessment of COVID-19 as per standard Siddha system of medicine principles and the occurrence of adverse effects will be documented as secondary outcomes. RANDOMISATION: The assignment to the study or control group will be allocated in equal numbers through randomization using random number generation in Microsoft Excel by a statistician who is not involved in the trial. The allocation scheme will be made by an independent statistician using a sealed envelope. The participants will be allocated immediately after the eligibility assessment and informed consent procedures. BLINDING (MASKING): This study is unblinded. The investigators will be blinded to data analysis, which will be carried out by a statistician who is not involved in the trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Sample size could not be calculated, as there is no prior trial on KSK. This trial will be a pilot trial. Hence, we intend to recruit 60 participants in total using a 1:1 allocation ratio, with 30 participants randomised into each arm. TRIAL STATUS: Protocol version 2.0 dated 16th May 2020. Recruitment is completed. The trial started recruitment on the 25th May 2020. We anticipate study including data analysis will finish on November 2020. We also stated that protocol was submitted before the end of data collection TRIAL REGISTRATION: The study protocol was registered with clinical trial registry of India (CTRI) with CTRI/2020/05/025215 on 16 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).