1. Lin LT, Hsu WC, Lin CC (2014) Antiviral natural products and herbal medicines. J Tradit Complement Med 4:24–35. https://doi.org/10.4103/2225-4110.124335
2. Li X, Wang W, Zhao X, et al (2020) Transmission dynamics and evolutionary history of 2019-nCoV. J Med Virol 92:501–511. https://doi.org/10.1002/jmv.25701
3. WHO (2021) Global research on coronavirus disease (COVID-19)
4. Rehman SU, Shafique L, Ihsan A, Liu Q (2020) Evolutionary trajectory for the emergence of novel coronavirus SARS-CoV-2. Pathogens 9:. https://doi.org/10.3390/pathogens9030240
5. Harcourt J, Tamin A, Lu X, et al (2020) Severe acute respiratory syndrome coronavirus 2 from patient with coronavirus disease, United States. Emerg Infect Dis 26:1266–1273. https://doi.org/10.3201/EID2606.200516
6. Wang W, Tang J, Wei F (2020) Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan, China. J Med Virol 92:441–447. https://doi.org/10.1002/jmv.25689
7. Chan JFW, Yuan S, Kok KH, et al (2020) A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 395:514–523. https://doi.org/10.1016/S0140-6736(20)30154-9
8. Li H, Liu Z, Ge J (2020) Scientific research progress of COVID-19/SARS-CoV-2 in the first five months. J. Cell. Mol. Med. 24:6558–6570
9. Udugama B, Kadhiresan P, Kozlowski HN, et al (2020) Diagnosing COVID-19: The Disease and Tools for Detection. ACS Nano 14:3822–3835
10. Carter LJ, Garner L V., Smoot JW, et al (2020) Assay Techniques and Test Development for COVID-19 Diagnosis. ACS Cent Sci 6:591–605. https://doi.org/10.1021/acscentsci.0c00501
11. Chilamakuri R, Agarwal S (2021) COVID-19: Characteristics and Therapeutics. Cells 10
12. Tchesnokov EP, Feng JY, Porter DP, Götte M (2019) Mechanism of inhibition of ebola virus RNA-dependent RNA polymerase by remdesivir. Viruses 11:. https://doi.org/10.3390/v11040326
13. Coomes EA, Haghbayan H (2020) Favipiravir, an antiviral for COVID-19? J. Antimicrob. Chemother. 75:2013–2014
14. Evans GB, Tyler PC, Schramm VL (2018) Immucillins in Infectious Diseases. ACS Infect. Dis. 4:107–117
15. Gong S, Su J, Yan X, et al (2020) Antiviral therapy for Coronavirus disease 2019. J. Cent. South Univ. (Medical Sci. 45:598–602
16. Wang XX, Luo BF, Jiang HJ, et al (2018) Recovery of natural killer cells is mainly in post-treatment period in chronic hepatitis C patients treated with sofosbuvir plus ledipasvir. World J. Gastroenterol. 24:4554–4564
17. Li F, Lu J, Ma X (2012) CPY3A4-mediated lopinavir bioactivation and its inhibition by ritonavir. Drug Metab Dispos 40:18–24. https://doi.org/10.1124/dmd.111.041400
18. Musarrat F, Chouljenko V, Dahal A, et al (2020) The anti-HIV drug nelfinavir mesylate (Viracept) is a potent inhibitor of cell fusion caused by the SARSCoV-2 spike (S) glycoprotein warranting further evaluation as an antiviral against COVID-19 infections. J Med Virol 92:2087–2095. https://doi.org/10.1002/jmv.25985
19. Li G, De Clercq E (2020) Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat. Rev. Drug Discov. 19:149–150
20. Chen J, Xia L, Liu L, et al (2020) Antiviral activity and safety of darunavir/Cobicistat for the treatment of COVID-19. Open Forum Infect Dis 7:. https://doi.org/10.1093/ofid/ofaa241
21. Chen H, Zhang Z, Wang L, et al (2020) First Clinical Study Using HCV Protease Inhibitor Danoprevir to Treat Naive and Experienced COVID-19 Patients. medRxiv 2020.03.22.20034041. https://doi.org/10.1101/2020.03.22.20034041
22. Satarker S, Ahuja T, Banerjee M, et al (2020) Hydroxychloroquine in COVID-19: Potential Mechanism of Action Against SARS-CoV-2. Curr. Pharmacol. Reports 6:203–211
23. Vankadari N (2020) Arbidol: A potential antiviral drug for the treatment of SARS-CoV-2 by blocking trimerization of the spike glycoprotein. Int J Antimicrob Agents 56:. https://doi.org/10.1016/j.ijantimicag.2020.105998
24. Bray M, Rayner C, Noël F, et al (2020) Ivermectin and COVID-19: A report in Antiviral Research, widespread interest, an FDA warning, two letters to the editor and the authors’ responses. Antiviral Res. 178
25. Zhou Q, Chen V, Shannon CP, et al (2020) Interferon-α2b Treatment for COVID-19. Front Immunol 11:. https://doi.org/10.3389/fimmu.2020.01061
26. Russell B, Moss C, George G, et al (2020) Associations between immune-suppressive and stimulating drugs and novel COVID-19 - A systematic review of current evidence. Ecancermedicalscience 14
27. Tu YF, Chien CS, Yarmishyn AA, et al (2020) A review of sars-cov-2 and the ongoing clinical trials. Int. J. Mol. Sci. 21
28. Masiá M, Fernández-González M, Padilla S, et al (2020) Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study. EBioMedicine 60:. https://doi.org/10.1016/j.ebiom.2020.102999
29. Wu D, Yang XO (2020) TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib. J Microbiol Immunol Infect 53:368–370. https://doi.org/10.1016/j.jmii.2020.03.005
30. Zhang X, Zhang Y, Qiao W, et al (2020) Baricitinib, a drug with potential effect to prevent SARS-COV-2 from entering target cells and control cytokine storm induced by COVID-19. Int. Immunopharmacol. 86
31. Baladia E, Pizarro AB, Ortiz-Muñoz L, Rada G (2020) Vitamin C for COVID-19: A living systematic review. Medwave 20:e7978. https://doi.org/10.5867/medwave.2020.06.7978
32. Mohan M, Cherian JJ, Sharma A (2020) Exploring links between Vitamin D deficiency and covid-19. PLoS Pathog 16:. https://doi.org/10.1371/journal.ppat.1008874
33. Acosta-Elias J, Espinosa-Tanguma R (2020) The Folate Concentration and/or Folic Acid Metabolites in Plasma as Factor for COVID-19 Infection. Front Pharmacol 11:. https://doi.org/10.3389/fphar.2020.01062
34. Aronson JK, Ferner RE (2020) Drugs and the renin-angiotensin system in covid-19. BMJ 369
35. Menendez JT (2016) The Mechanism of Action of LCZ696. Card Fail Rev 2:40. https://doi.org/10.15420/cfr.2016:1:1
36. Rismanbaf A (2020) Potential Treatments for COVID-19; a Narrative Literature Review. Arch Acad Emerg Med 8:2–4. https://doi.org/10.22037/aaem.v8i1.596
37. Echeverría-Esnal D, Martin-Ontiyuelo C, Navarrete-Rouco ME, et al (2021) Azithromycin in the treatment of COVID-19: a review. Expert Rev. Anti. Infect. Ther. 19:147–163
38. Parra-Medina R, Sarmiento-Monroy JC, Rojas-Villarraga A, et al (2020) Colchicine as a possible therapeutic option in COVID-19 infection. Clin. Rheumatol. 39:2485–2486
39. Liu J, Zheng X, Huang Y, et al (2020) Successful use of methylprednisolone for treating severe COVID-19. J Allergy Clin Immunol 146:325–327. https://doi.org/10.1016/j.jaci.2020.05.021
40. Wongrakpanich S, Wongrakpanich A, Melhado K, Rangaswami J (2018) A comprehensive review of non-steroidal anti-inflammatory drug use in the elderly. Aging Dis. 9:143–150
41. Lane TR, Massey C, Comer JE, et al (2019) Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection. PLoS Negl Trop Dis 13:. https://doi.org/10.1371/journal.pntd.0007890
42. Mathias AA, German P, Murray BP, et al (2010) Pharmacokinetics and pharmacodynamics of gs-9350: A novel pharmacokinetic enhancer without Anti-HIV activity. Clin Pharmacol Ther 87:322–329. https://doi.org/10.1038/clpt.2009.228
43. Nitulescu GM, Paunescu H, Moschos SA, et al (2020) Comprehensive analysis of drugs to treat SARS-CoV-2 infection: Mechanistic insights into current COVID-19 therapies (Review). Int. J. Mol. Med. 46:467–488
44. Seifirad S (2020) Pirfenidone: A novel hypothetical treatment for COVID-19. Med Hypotheses 144:. https://doi.org/10.1016/j.mehy.2020.110005
45. Lin MH, Moses DC, Hsieh CH, et al (2018) Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes. Antiviral Res 150:155–163. https://doi.org/10.1016/j.antiviral.2017.12.015
46. Sanchez-Pernaute O, Romero-Bueno FI, Selva-O’Callaghan A (2020) Why Choose Cyclosporin A as First-line Therapy in COVID-19 Pneumonia. Reumatol. Clin.
47. Soliman A, Fathy A, Khashab S, et al (2013) Sirolimus conversion may suppress viral replication in hepatitis C virus-positive renal transplant candidates. Exp Clin Transplant 11:408–411. https://doi.org/10.6002/ect.2013.0017
48. Chen X, Kopecky DJ, Mihalic J, et al (2012) Structure-guided design, synthesis, and evaluation of guanine-derived inhibitors of the eIF4E mRNA-cap interaction. J Med Chem 55:3837–3851. https://doi.org/10.1021/jm300037x
49. Yiğenoğlu TN, Hacıbekiroğlu T, Berber İ, et al (2020) Convalescent plasma therapy in patients with COVID-19. J. Clin. Apher. 35:367–373
50. Yuan H, Ma Q, Ye L, Piao G (2016) The traditional medicine and modern medicine from natural products. Molecules 21:. https://doi.org/10.3390/molecules21050559
51. Walsh CT, Tang Y (2017) Natural Product Biosynthesis. The Royal Society of Chemistry
52. Martin YC, Kofron JL, Traphagen LM (2002) Do structurally similar molecules have similar biological activity? J Med Chem 45:4350–4358. https://doi.org/10.1021/jm020155c
53. Gfeller D, Grosdidier A, Wirth M, et al (2014) SwissTargetPrediction: A web server for target prediction of bioactive small molecules. Nucleic Acids Res 42:. https://doi.org/10.1093/nar/gku293
54. Kumar A, Zhang KYJ (2018) Advances in the development of shape similarity methods and their application in drug discovery. Front. Chem. 6
55. Nobile MS, Cazzaniga P, Tangherloni A, Besozzi D (2017) Graphics processing units in bioinformatics, computational biology and systems biology. Brief Bioinform 18:870–885. https://doi.org/10.1093/bib/bbw058
56. Aditya Rao SJ, Ramesh CK, Raghavendra S, Paramesha M (2020) Dehydroabietylamine, A Diterpene from Carthamus tinctorious L. Showing Antibacterial and Anthelmintic Effects with Computational Evidence. Curr Comput Aided Drug Des 16:231–237. https://doi.org/10.2174/1573409915666190301142811
57. Gange SJ, Golub ET (2016) From smallpox to big data: The next 100 years of epidemiologic methods. Am. J. Epidemiol. 183:423–426
58. Docherty AB, Lone NI (2015) Exploiting big data for critical care research. Curr. Opin. Crit. Care 21:467–472
59. Greene CS, Tan J, Ung M, et al (2014) Big data bioinformatics. J. Cell. Physiol. 229:1896–1900
60. Wasser T, Haynes K, Barron J, Cziraky M (2015) Using “big data” to validate claims made in the pharmaceutical approval process. J Med Econ 18:1013–1019. https://doi.org/10.3111/13696998.2015.1108919
61. Raghavendra S, Aditya Rao SJ, Kumar V, Ramesh CK (2015) Multiple ligand simultaneous docking (MLSD): A novel approach to study the effect of inhibitors on substrate binding to PPO. Comput Biol Chem 59:81–86. https://doi.org/10.1016/j.compbiolchem.2015.09.008
62. Janakirama ARS, Shivayogi SM, Satyanarayana JK, Kumaran RC (2020) Characterization of isolated compounds from Morus spp. and their biological activity as anticancer molecules. BioImpacts. https://doi.org/10.34172/bi.2021.09
63. Arantes PR, Saha A, Palermo G (2020) Fighting covid-19 using molecular dynamics simulations. ACS Cent Sci 6:1654–1656. https://doi.org/10.1021/acscentsci.0c01236
64. Dr. Duke’s phytochemical and ethnobotanical databases. US Dep Agric Agric Res Serv 1992-2016. https://doi.org/http://dx.doi.org/10.15482/USDA.ADC/1239279
65. Zeng X, Zhang P, He W, et al (2018) NPASS: Natural product activity and species source database for natural product research, discovery and tool development. Nucleic Acids Res 46:D1217–D1222. https://doi.org/10.1093/nar/gkx1026
66. Kim S, Chen J, Cheng T, et al (2019) PubChem 2019 update: Improved access to chemical data. Nucleic Acids Res 47:D1102–D1109. https://doi.org/10.1093/nar/gky1033
67. U.S. National Institute of Health (NIH), U.S. National Library of Medicine (NLM) (2008) ClinicalTrials.gov database. In: U.S. Natl. Libr. Med. https://clinicaltrials.gov/ct2/home
68. Sander T, Freyss J, Von Korff M, Rufener C (2015) DataWarrior: An open-source program for chemistry aware data visualization and analysis. J Chem Inf Model 55:460–473. https://doi.org/10.1021/ci500588j
69. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 23:3–25
70. Doak BC, Over B, Giordanetto F, Kihlberg J (2014) Oral druggable space beyond the rule of 5: Insights from drugs and clinical candidates. Chem. Biol. 21:1115–1142
71. Aditya R, Venugopal T, Jayanna N, et al (2020) Bioactive isolates of Morus species as antibacterial agents and their insilico profiling. Lett Drug Des Discov 17:. https://doi.org/10.2174/1570180817999201104120815
72. Jarrahpour A, Motamedifar M, Zarei M, et al (2010) Petra, Osiris, and Molinspiration Together as a Guide in Drug Design: Predictions and Correlation Structure/Antibacterial Activity Relationships of New N-Sulfonyl Monocyclic β-Lactams. Phosphorus Sulfur Silicon Relat Elem 185:491–497. https://doi.org/10.1080/10426500902953953
73. Cheng F, Li W, Zhou Y, et al (2012) AdmetSAR: A comprehensive source and free tool for assessment of chemical ADMET properties. J Chem Inf Model 52:3099–3105. https://doi.org/10.1021/ci300367a
74. Trott O, Olson AJ (2010) Software news and update AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455–461. https://doi.org/10.1002/jcc.21334
75. Lin J-H (2012) Accommodating Protein Flexibility for Structure-Based Drug Design. Curr Top Med Chem 11:171–178. https://doi.org/10.2174/156802611794863580
76. Salsbury FR (2010) Molecular dynamics simulations of protein dynamics and their relevance to drug discovery. Curr. Opin. Pharmacol. 10:738–744
77. Schmid N, Eichenberger AP, Choutko A, et al (2011) Definition and testing of the GROMOS force-field versions 54A7 and 54B7. Eur Biophys J 40:843–856. https://doi.org/10.1007/s00249-011-0700-9
78. Abraham MJ, Murtola T, Schulz R, et al (2015) Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1–2:19–25. https://doi.org/10.1016/j.softx.2015.06.001
79. Berendsen HJC, Postma JPM, van Gunsteren WF, Hermans J (1981) Interaction Models for Water in Relation to Protein Hydration. pp 331–342
80. Bussi G, Donadio D, Parrinello M (2007) Canonical sampling through velocity rescaling. J Chem Phys 126:. https://doi.org/10.1063/1.2408420
81. Parrinello M, Rahman A (1981) Polymorphic transitions in single crystals: A new molecular dynamics method. J Appl Phys 52:7182–7190. https://doi.org/10.1063/1.328693
82. Hess B, Bekker H, Berendsen HJC, Fraaije JGEM (1997) LINCS: A Linear Constraint Solver for molecular simulations. J Comput Chem 18:1463–1472. https://doi.org/10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H
83. Essmann U, Perera L, Berkowitz ML, et al (1995) A smooth particle mesh Ewald method. J Chem Phys 103:8577–8593. https://doi.org/10.1063/1.470117
84. Kumari R, Kumar R, Consortium OSDD, Lynn A (2014) g _ mmpbsa - A GROMACS tool for MM-PBSA and its optimization for high-throughput binding energy calculations. J Chem Inf Model 54:1951–1962
85. Kwofie SK, Broni E, Teye J, et al (2019) Pharmacoinformatics-based identification of potential bioactive compounds against Ebola virus protein VP24. Comput Biol Med 113:. https://doi.org/10.1016/j.compbiomed.2019.103414
86. Suenderhauf C, Hammann F, Huwyler J (2012) Computational prediction of blood-brain barrier permeability using decision tree induction. Molecules 17:10429–10445. https://doi.org/10.3390/molecules170910429
87. Yuki K, Fujiogi M, Koutsogiannaki S (2020) COVID-19 pathophysiology: A review. Clin. Immunol. 215
88. Sheu TG, Deyde VM, Okomo-Adhiambo M, et al (2008) Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide from 2004 to 2008. Antimicrob Agents Chemother 52:3284–3292. https://doi.org/10.1128/AAC.00555-08
89. Geretti AM, Armenia D, Ceccherini-Silberstein F (2012) Emerging patterns and implications of HIV-1 integrase inhibitor resistance. Curr. Opin. Infect. Dis. 25:677–686
90. Dyall J, Coleman CM, Hart BJ, et al (2014) Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother 58:4885–4893. https://doi.org/10.1128/AAC.03036-14
91. Cao H, Zhang Y, Zhao J, et al (2017) Prediction of the Ebola Virus Infection Related Human Genes Using Protein-Protein Interaction Network. Comb Chem High Throughput Screen 20:. https://doi.org/10.2174/1386207320666170310114816
92. Barrows NJ, Campos RK, Powell ST, et al (2016) A Screen of FDA-Approved Drugs for Inhibitors of Zika Virus Infection. Cell Host Microbe 20:259–270. https://doi.org/10.1016/j.chom.2016.07.004
93. Islam MT, Sarkar C, El-Kersh DM, et al (2020) Natural products and their derivatives against coronavirus: A review of the non-clinical and pre-clinical data. Phyther. Res. 34:2471–2492
94. Prasansuklab A, Theerasri A, Rangsinth P, et al (2021) Anti-COVID-19 drug candidates: A review on potential biological activities of natural products in the management of new coronavirus infection. J. Tradit. Complement. Med. 11:144–157
95. Huang J, Tao G, Liu J, et al (2020) Current Prevention of COVID-19: Natural Products and Herbal Medicine. Front. Pharmacol. 11
96. Gasmi A, Chirumbolo S, Peana M, et al (2021) The Role of Diet and Supplementation of Natural Products in COVID-19 Prevention. Biol Trace Elem Res. https://doi.org/10.1007/s12011-021-02623-3
97. Chakravarti R, Singh R, Ghosh A, et al (2021) A review on potential of natural products in the management of COVID-19. RSC Adv. 11:16711–16735