Please cite this article in press Piratheepkumar. R and Vijitha. P, Role of Natural Product In Preventing Covid-19.., Indo Am. J. P. Sci, 2021; 08(9).

1. Jamuna D, Sathiyarajeswaran P, Devi MS, Kanakavalli K, Vinod NP, Nirmala A, Ravikumar T, Pathiban P, Babu K, Dhanam C. Survival analysis to assess the length of stay of novel coronavirus (COVID-19) patients under Integrated Medicine-Zinc, Vitamin C &KabasuraKudineer (ZVcKK). European Journal of Molecular & Clinical Medicine. 2021 Jan 13;7(10):1375-87.
2. Chitra SM, Mallika P, Anbu N, NarayanaBabu R, SugunaBai A, Raj RD, Premnath D. An Open Clinical Evaluation Of Selected Siddha Regimen In Expediting The Management Of Covid-19–A Randomized Controlled Study. Journal of Ayurveda and Integrative Medicine. 2021 Jan 21.
3. Wilson E, Vinayak S, Kanakavalli K. Siddha and Biomedicine Integrative Management of Novel Corona Virus Disease-A Case Report. International Journal of AYUSH Case Reports. 2020 Sep 29;4(3):154-60.
4. Kiran G, Karthik L, Devi MS, Sathiyarajeswaran P, Kanakavalli K, Kumar KM, Kumar DR. In silico computational screening of KabasuraKudineer-official Siddha formulation and JACOM against SARS-CoV-2 spike protein. Journal of Ayurveda and integrative medicine. 2020 May 25.
5. Mekala P, Murthy TG. Phytochemical screening and pharmacological update on KabasuraKudineerChoornam and NilavembuKudineerChoornam. Journal of Pharmacognosy and Phytochemistry. 2020;9(3):1031-6.
6. Pitchiah Kumar M, Meenakshi Sundaram K, Ramasamy MS. Coronavirus spike (S) glycoprotein (2019-ncov) targeted siddha medicines kabasurakudineer and thonthasurakudineer–in silico evidence for corona viral drug. Asian J. Pharm. Res. Health Care. 2020:20-7.
7. Walter TM, Justinraj CS, Nandini VS. Effect of Nilavembukudineer in the Prevention and Management of COVID–19 by inhibiting ACE2 Receptor. Siddha Papers. 2020;15(2).
8. Sathiyarajeswaran P, Devi MSS, Narayana SKK, Manoharn MT, DurairajS,Sundaramoorty B, Dhanaraj K, Patturayan R. Quality Standards for UraiMathirai – A Siddha Immunomodulator Formulation for Children. JPhytopharmacol 2018; 7(1):40-44.
9. Geir Hetland, Egil Johnson, Soosaipillai V. Bernardshaw, Bjørn Grinde. Can medicinal mushrooms have prophylactic or therapeutic effect against COVID‐19 and its pneumonic superinfection and complicating inflammation. Scand J Immunol. 2020;00:e12937 10.1111/sji.12937
10. Shah, Bhumi and P, Sathiyarajeswaran and MS, Shree Devi and K, Kanakavalli and Narayanan, Kirubakaran and L, Karthik, Repurposing of Medicinal Plants Used in Siddha Formulations As Potential Protease Inhibitors of COVID-19: An in silico Approach (July 13, 2020).
11. S. Thillaivanan et.al. A Review On “Kapa Sura Kudineer”-A Siddha Formulary Prediction For Swine Flu: International Journal of Pharmaceutical Sciences and Drug Research 2015; 7(5): 376-383
12. Siva Lakshmi S, Kumari Hv, Mohan S, Meenakumari R. Therapeutic Effectiveness Of The Siddha Immuno Modulatory Polyherbal Formulation NellikaiLegiyam Against Covid-19 Pandemic-A Review.
13. Gupta H, Gupta M, Bhargava S. Potential use of turmeric in COVID‐19. Clinical and experimental Dermatology. 2020 Oct;45(7):902-3.
14. John A, Jayachandran R, Ethirajulu S, Sathiyarajeswaran P. Analysis Of Kabasurakudineer Chooranam-A Siddha Formulation. International Ayurvedic Medical Journal. 2015 Sep;3(9):2915-20.
15. Rajalakshmi S, Samraj K, Sathiyarajeswaran P, Kanagavalli K. Preparedness of Siddha system of medicine in practitioner perspective during a pandemic outbreak with special reference to COVID-19. CELLMED. 2020;10(4):29-1.
16. Meenakumari R. Siddha Preventive and Clinical Management for COVID-19. Journal of Siddha. 2020;4(1).
17. Swetha R, Premavathy D. Siddha based decoctions better remedy to overcome COVID-19-a review. International Journal of Current Research and Review. 2020 Jan 1;12(21 Special Issue).
18. Anand Ganapathy A, Alaganandam Kumaran, Lekha G S;Prevention of COVID 19 – Siddha perspective; International Journal of Ayurvedic Medicine, Vol 11 (4), 594-615
19. S. Radha, S. P. Rajalakshmi, K. Subash, K. Samraj: A Perspective Review On Siddha System Of Medicine In The Management Of Corona Virus Disease 2019;Journal Of Natural Remedies: Vol 21(2), April 2021;Pp. 110-123
20. Rathinam, S., Muthiah, K., Parameswaran, S., Tamilarasan, K., Selvarajan, E., &Ayyasamy, U. (2020). Analogy of KabaSuram with COVID-19 Symptoms – A Siddha Literature Review. International Journal of Ayurvedic Medicine, 11(4), 616-621.
21. Ksiazek T.G., Erdman D., Goldsmith C.S., Zaki S.R., Peret T., Emery S., Tong S., Urbani C., Comer J.A., Lim W., Rollin P.E., Dowell S.F., Ling A.E., Humphrey C.D., Shieh W.J., Guarner J., Paddock C.D., Rota P., Fields B., DeRisi J., Yang J.Y., Cox N., Hughes J.M., LeDuc J.W., Bellini W.J., Anderson L.J., SW Group A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003;348:1953–1966.
22. Li Q., Guan X., Wu P., Wang X., Zhou L., Tong Y., Ren R., Leung K.S.M., Lau E.H.Y., Wong J.Y., Xing X., Xiang N., Wu Y., Li C., Chen Q., Li D., Liu T., Zhao J., Liu M., Tu W., Chen C., Jin L., Yang R., Wang Q., Zhou S., Wang R., Liu H., Luo Y., Liu Y., Shao G., Li H., Tao Z., Yang Y., Deng Z., Liu B., Ma Z., Zhang Y., Shi G., Lam T.T.Y., Wu J.T., Gao G.F., Cowling B.J., Yang B., Leung G.M., Feng Z. Early transmission dynamics in Wuhan, China, of Novel Coronavirus-infected pneumonia. N Engl J Med. 2020;382:1199–1207.
23. Zheng M., Gao Y., Wang G., Song G., Liu S., Sun D., Xu Y., Tian Z. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020 doi: 10.1038/s41423-020-0402-2.
24. Zhang J., Litvinova M., Wang W., Wang Y., Deng X., Chen X., Li M., Zheng W., Yi L., Chen X., Wu Q., Liang Y., Wang X., Yang J., Sun K., Longini I.M., Jr., Halloran M.E., Wu P., Cowling B.J., Merler S., Viboud C., Vespignani A., Ajelli M., Yu H. Evolving epidemiology and transmission dynamics of coronavirus disease 2019 outside Hubei province, China: a descriptive and modelling study. Lancet Infect Dis. 2020 doi: 10.1016/S1473-3099(20)30230-9.
25. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G., Xu J., Gu X., Cheng Z., Yu T., Xia J., Wei Y., Wu W., Xie X., Yin W., Li H., Liu M., Xiao Y., Gao H., Guo L., Xie J., Wang G., Jiang R., Gao Z., Jin Q., Wang J., Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
26. Shi H., Han X., Jiang N., Cao Y., Alwalid O., Gu J., Fan Y., Zheng C. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. 2020;20:425–434.
27. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., Xiang J., Wang Y., Song B., Gu X., Guan L., Wei Y., Li H., Wu X., Xu J., Tu S., Zhang Y., Chen H., Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062.
28. Lu X., Zhang L., Du H., Zhang J., Li Y.Y., Qu J., Zhang W., Wang Y., Bao S., Li Y., Wu C., Liu H., Liu D., Shao J., Peng X., Yang Y., Liu Z., Xiang Y., Zhang F., Silva R.M., Pinkerton K.E., Shen K., Xiao H., Xu S., Wong G.W.K., T Chinese Pediatric Novel Coronavirus Study SARS-CoV-2 infection in children. N Engl J Med. 2020 doi: 10.1056/NEJMc2005073.
29. Qiu H., Wu J., Hong L., Luo Y., Song Q., Chen D. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. Lancet Infect Dis. 2020 doi: 10.1016/S1473-3099(20)30198-5.
30. Cao B. A trial of Lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020 doi: 10.1056/NEJMoa2001282.
31. Gautret P., Lagier J.C., Parola P., Hoang V.T., Meddeb L., Mailhe M., Doudier B., Courjon J., Giordanengo V., Vieira V.E., Dupont H.T., Honore S., Colson P., Chabriere E., La Scola B., Rolain J.M., Brouqui P., Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;105949
32. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., Qiu Y., Wang J., Liu Y., Wei Y., Xia J., Yu T., Zhang X., Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–513.
33. Wu Z., McGoogan J.M. Characteristics of and important lessons from the Coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 doi: 10.1001/jama.2020.2648.
34. Onder G., Rezza G., Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020 doi: 10.1001/jama.2020.4683.
35. Du Y., Tu L., Zhu P., Mu M., Wang R., Yang P., Wang X., Hu C., Ping R., Hu P., Li T., Cao F., Chang C., Hu Q., Jin Y., Xu G. Clinical features of 85 fatal cases of COVID-19 from Wuhan: a retrospective observational Study. Am J Respir Crit Care Med. 2020 doi: 10.1164/rccm.202003-0543OC.
36. Gao Y., Li T., Han M., Li X., Wu D., Xu Y., Zhu Y., Liu Y., Wang X., Wang L. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. J Med Virol. 2020 doi: 10.1002/jmv.25770.
37. Li W., Moore M.J., Vasilieva N., Sui J., Wong S.K., Berne M.A., Somasundaran M., Sullivan J.L., Luzuriaga K., Greenough T.C., Choe H., Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Journal. 2003;426:450–454.
38. Chen Y., Guo Y., Pan Y., Zhao Z.J. Structure analysis of the receptor binding of 2019-nCoV. Journal. 2020 doi: 10.1016/j.bbrc.2020.02.071.
39. Walls A.C., Park Y.J., Tortorici M.A., Wall A., McGuire A.T., Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Journal. 2020 doi: 10.1016/j.cell.2020.02.058.
40. Letko M., Marzi A., Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Journal. 2020;5:562–569.
41. Zou X., Chen K., Zou J., Han P., Hao J., Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Journal. 2020 doi: 10.1007/s11684-020-0754-0
42. Belouzard S., Chu V.C., Whittaker G.R. Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Journal. 2009;106:5871–5876.
43. Millet J.K., Whittaker G.R. Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein. Journal. 2014;111:15214–15219.
44. Ou X., Liu Y., Lei X., Li P., Mi D., Ren L., Guo L., Guo R., Chen T., Hu J., Xiang Z., Mu Z., Chen X., Chen J., Hu K., Jin Q., Wang J., Qian Z. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Journal. 2020;11:1620
45. Belouzard S., Millet J.K., Licitra B.N., Whittaker G.R. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Journal. 2012;4:1011–1033.
46. Hoffmann M., Kleine-Weber H., Schroeder S., Kruger N., Herrler T., Erichsen S., Schiergens T.S., Herrler G., Wu N.H., Nitsche A., Muller M.A., Drosten C., Pohlmann S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Journal. 2020 doi: 10.1016/j.cell.2020.02.052.
47. Guan W.J., Ni Z.Y., Hu Y., Liang W.H., Ou C.Q., He J.X., Liu L., Shan H., Lei C.L., Hui D.S.C., Du B., Li L.J., Zeng G., Yuen K.Y., Chen R.C., Tang C.L., Wang T., Chen P.Y., Xiang J., Li S.Y., Wang J.L., Liang Z.J., Peng Y.X., Wei L., Liu Y., Hu Y.H., Peng P., Wang J.M., Liu J.Y., Chen Z., Li G., Zheng Z.J., Qiu S.Q., Luo J., Ye C.J., Zhu S.Y., Zhong N.S., C China Medical Treatment Expert Group for Clinical characteristics of coronavirus disease 2019 in China. Journal. 2020 doi: 10.1056/NEJMoa2002032.
48. Hamming I., Timens W., Bulthuis M.L., Lely A.T., Navis G., van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. Journal. 2004;203:631–637.
49. Jia H.P., Look D.C., Shi L., Hickey M., Pewe L., Netland J., Farzan M., Wohlford-Lenane C., Perlman S., McCray P.B., Jr. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. Journal. 2005;79:14614–14621.
50. Yoshikawa T., Hill T., Li K., Peters C.J., Tseng C.T. Severe acute respiratory syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells. Journal. 2009;83:3039–3048.
51. Fujimoto I., Pan J., Takizawa T., Nakanishi Y. Virus clearance through apoptosis-dependent phagocytosis of influenza A virus-infected cells by macrophages. Journal. 2000;74:3399–3403.
52. Jeffers S.A., Tusell S.M., Gillim-Ross L., Hemmila E.M., Achenbach J.E., Babcock G.J., Thomas W.D., Jr., Thackray L.B., Young M.D., Mason R.J., Ambrosino D.M., Wentworth D.E., Demartini J.C., Holmes K.V. CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Journal. 2004;101:15748–15753.
53. Marzi A., Gramberg T., Simmons G., Moller P., Rennekamp A.J., Krumbiegel M., Geier M., Eisemann J., Turza N., Saunier B., Steinkasserer A., Becker S., Bates P., Hofmann H., Pohlmann S. DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and the S protein of severe acute respiratory syndrome coronavirus. Journal. 2004;78:12090–12095.
54. Yang Z.Y., Huang Y., Ganesh L., Leung K., Kong W.P., Schwartz O., Subbarao K., Nabel G.J. pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN. Journal. 2004;78:5642–5650.
55. Zhou Y., Fu B., Zheng X., Wnag D., Zhao C., Qi Y., Sun R., Tian Z., Xu X., Wei H. Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients. Journal. 2020
56. Qin C., Zhou L., Hu Z., Zhang S., Yang S., Tao Y., Xie C., Ma K., Shang K., Wang W., Tian D.S. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Journal. 2020 doi: 10.1093/cid/ciaa248.
57. Huang H., Wang S., Jiang T., Fan R., Zhang Z., Mu J., Li K., Wang Y., Jin L., Lin F., Xia J., Sun L., Xu B., Ji C., Chen J., Chang J., Tu B., Song B., Zhang C., Wang F.S., Xu R. High levels of circulating GM-CSF(+)CD4(+) T cells are predictive of poor outcomes in sepsis patients: a prospective cohort study. Journal. 2019;16:602–610.
58. Liu S., Su X., Pan P., Zhang L., Hu Y., Tan H., Wu D., Liu B., Li H., Li H., Li Y., Dai M., Li Y., Hu C., Tsung A. Neutrophil extracellular traps are indirectly triggered by lipopolysaccharide and contribute to acute lung injury. Journal. 2016;6:37252.
59. Koutsogiannaki S., Shimaoka M., Yuki K. The use of volatile anesthetics as sedatives for acute respiratory distress syndrome. Journal. 2019;6:27–38.
60. Fang M., Siciliano N.A., Hersperger A.R., Roscoe F., Hu A., Ma X., Shamsedeen A.R., Eisenlohr L.C., Sigal L.J. Perforin-dependent CD4+ T-cell cytotoxicity contributes to control a murine poxvirus infection. Journal. 2012;109:9983–9988.
61. Small B.A., Dressel S.A., Lawrence C.W., Drake D.R., 3rd, Stoler M.H., Enelow R.I., Braciale T.J. CD8(+) T cell-mediated injury in vivo progresses in the absence of effector T cells. Journal. 2001;194:1835–1846.
62. Wang M., Hao H., Leeper N.J., Zhu L., Early Career C. Thrombotic regulation from the endothelial cell perspectives. Journal. 2018;38:e90–e95.
63. Zeng H., Pappas C., Belser J.A., Houser K.V., Zhong W., Wadford D.A., Stevens T., Balczon R., Katz J.M., Tumpey T.M. Human pulmonary microvascular endothelial cells support productive replication of highly pathogenic avian influenza viruses: possible involvement in the pathogenesis of human H5N1 virus infection. Journal. 2012;86:667–678.
64. Liu Y., Yan L.M., Wan L., Xiang T.X., Le A., Liu J.M., Peiris M., Poon L.L.M., Zhang W. Viral dynamics in mild and severe cases of COVID-19. Journal. 2020 doi: 10.1016/S1473-3099(20)30232-2.
65. Patel S.K., Velkoska E., Burrell L.M. Emerging markers in cardiovascular disease: where does angiotensin-converting enzyme 2 fit in? Journal. 2013;40:551–559.
66. Saule P., Trauet J., Dutriez V., Lekeux V., Dessaint J.P., Labalette M. Accumulation of memory T cells from childhood to old age: central and effector memory cells in CD4(+) versus effector memory and terminally differentiated memory cells in CD8(+) compartment. Journal. 2006;127:274–281.
67. Li M., Yao D., Zeng X., Kasakovski D., Zhang Y., Chen S., Zha X., Li Y., Xu L. Age related human T cell subset evolution and senescence. Journal. 2019;16:24.
68. Connors T.J., Ravindranath T.M., Bickham K.L., Gordon C.L., Zhang F., Levin B., Baird J.S., Farber D.L. Airway CD8(+) T cells are associated with lung injury during infant viral respiratory tract infection. Journal. 2016;54:822–830.
69. Smits S.L., de Lang A., van den Brand J.M., Leijten L.M., Eijkemans M.J., van Amerongen G., Kuiken T., Andeweg A.C., Osterhaus A.D., Haagmans B.L. Exacerbated innate host response to SARS-CoV in aged non-human primates. Journal. 2010;6
70. Roberts A., Deming D., Paddock C.D., Cheng A., Yount B., Vogel L., Herman B.D., Sheahan T., Heise M., Genrich G.L., Zaki S.R., Baric R., Subbarao K. A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice. Journal. 2007;3
71. Wong H.R., Freishtat R.J., Monaco M., Odoms K., Shanley T.P. Leukocyte subset-derived genomewide expression profiles in pediatric septic shock. Journal. 2010;11:349–355.
72. Nickbakhsh S., Mair C., Matthews L., Reeve R., Johnson P.C.D., Thorburn F., von Wissmann B., Reynolds A., McMenamin J., Gunson R.N., Murcia P.R. Virus-virus interactions impact the population dynamics of influenza and the common cold. Journal. 2019 doi: 10.1073/pnas.1911083116.
73. Beauchemin K.J., Wells J.M., Kho A.T., Philip V.M., Kamir D., Kohane I.S., Graber J.H., Bult C.J. Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development. Journal. 2016;4
74. M. Lipsitch, D. L. Swerdlow, and L. Finelli, “Defining the epidemiology of Covid-19-studies needed,” New England Journal of Medicine, vol. 382, no. 13, pp. 1194–1196, 2020.
75. A. Cheepsattayakorn and R. Cheepsattayakorn, “Proximal origin and phylogenetic analysis of COVID-19 (2019-nCoV or SARS-CoV-2),” EC Microbiology, vol. 19, pp. 9–12, 2020.
76. World Health Organization, Coronavirus Disease 2019, World Health Organization, Geneva, Switzerland, 2020, https://www.who.int/emergencies/diseases/novel-coronavirus-2019.