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Licensed Unlicensed Requires Authentication Published online by De Gruyter October 22, 2021

Arq Ajīb – a wonder Unani formulation for inhibiting SARS-CoV-2 spike glycoprotein and main protease – an in silico approach

N. Zaheer Ahmed , G. Dicky John Davis , Asim Ali Khan , Lavanya Prabhakar , Meena Ram Paratap , Zeba Afnaan , Meera Devi Sri and Noman Anwar ORCID logo EMAIL logo



The current pandemic caused by Severe Acute Respiratory Syndrome Corona-Virus 2 (SARS-CoV-2) has become a global health menace with significant morbidity and mortality besides huge socioeconomic implications. Despite the approval of few vaccines for the prevention of the disease, the discovery of safe and effective countermeasures especially from natural sources is of paramount importance, as the number of cases continues escalating. Arq Ajīb has long been used for various diseases and its ingredients have been reported for antiviral, antimicrobial, antipyretic, anti-inflammatory, antioxidant activities. The present study investigates the inhibitory effect of phytocompound of Arq Ajīb on potential drug targets of SARS-CoV-2.


The structures of phytocompounds present in Arq Ajīb were retrieved from PubChem database and some were illustrated using Marvin Sketch. SARS-CoV-2 S glycoprotein (PDB ID: 6LZG) and 3CLpro (PDB ID: 7BQY) were selected as the target protein. Dock Prep module in UCSF Chimera software was used for receptor structure processing. AutoDock Vina was used to calculate the binding affinities between the protein and ligands and to predict most promising compounds with best scores.


Molecular docking results predicted that the phytocompounds of Arq Ajīb had good binding affinity and interaction with S glycoprotein and 3CLpro. Quercetin and Isorhoifolin from Mentha arvensis were identified as promising candidates with the potential to interact with 3CLpro and spike glycoprotein and inhibit the viral replication and its entry into the host.


Arq Ajīb may prove valuable for developing novel therapeutic candidate for COVID-19; however, it has to be substantiated further with in-vitro and in-vivo studies.

Corresponding author: Dr. Noman Anwar, Research Officer (Unani), Regional Research Institute of Unani Medicine, N1, West Mada Church Road, Royapuram, Chennai600013, Tamil Nadu, India, E-mail:

Funding source: Central Council for Research in Unani Medicine


Authors acknowledge Director General, CCRUM, Ministry of Ayush, Govt. of India for financial support for this study.

  1. Research funding: Central Council for Research in Unani Medicine, New Delhi, Ministry of Ayush, Govt. of India.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: The authors declare no competing interests

  4. Ethical declaration: The present study is a preliminary computational study and does not involve any animal or human subjects; hence it does not involve any ethical and legal dimensions.


1. Wang, C, Horby, PW, Hayden, FG, Gao, GF. A novel coronavirus outbreak of global health concern. Lancet 2020;395:470–3. in Google Scholar

2. World Health Organization. Coronavirus disease (COVID-19) pandemic; 2021. Available from: in Google Scholar

3. Reuters. Asia Pacific: India’s daily COVID-19 cases pass 400,000 for first time as second wave worsens; 2021. Available from: in Google Scholar

4. World Health Organization. World health emergency dashboard: WHO (COVID-19) homepage; 2021. Available from: in Google Scholar

5. Zheng, J. SARS-CoV-2: an emerging coronavirus that causes a global threat. Int J Biol Sci 2020;16:1678–85. in Google Scholar PubMed PubMed Central

6. Nikhat, S, Fazil, M. Overview of Covid-19; its prevention and management in the light of Unani medicine. Sci Total Environ 2020;728:138859. in Google Scholar PubMed PubMed Central

7. Wang, Q, Zhang, Y, Wu, L, Niu, S, Song, C, Zhang, Z, et al.. Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell 2020;181:894–904. in Google Scholar PubMed PubMed Central

8. Ismail, EM, Shantier, SW, Mohammed, MS, Musa, HH, Osman, W, Mothana, RA. Quinoline and quinazoline alkaloids against COVID-19: an in silico multitarget approach. J Chem 2021;2021:e3613268. in Google Scholar

9. Mukherjee, PK. Antiviral evaluation of herbal drugs. Qual Control Eval Herbal Drugs 2019;599–628. PMC7149824Search in Google Scholar PubMed

10. Kiran, G, Karthik, L, Shree Devi, MS, Sathiyarajeswaran, P, Kanakavalli, K, Kumar, KM, et al.. In silico computational screening of KabasuraKudineer - official Siddha formulation and JACOM against SARS-CoV-2 spike protein. J Ayurveda Integr Med 2020;2520:S097530024–94763. in Google Scholar PubMed PubMed Central

11. CCRUM, Govt. of India. The Unani pharmacopoeia of India, part 2, 1st ed. New Delhi: Central Council for Research in Unani Medicine; 2009, vol 1:5–6 pp.Search in Google Scholar

12. Khan, A. Qarabadeen Azam -o- Akmal (Urdu translation). New Delhi: Central Council for Research in Unani Medicine; 2005:405 p.Search in Google Scholar

13. CCRUM, Govt. of India. Qarabadeen Jadeed. New Delhi: Central Council for Research in Unani Medicine; 2005:152–3 pp.Search in Google Scholar

14. Anwar, N, Ahmed, NZ, Begum, S. Plausible role of Arq Ajib in combating COVID-19: a multifaceted review. J Drug Deliv Therapeut 2021;11:141–8. in Google Scholar

15. Khan, MA, Khan, NA, Qasmi, IA, Ahmad, G, Zafar, S. Protective effect of Arque-Ajeeb on acute experimental diarrhoea in rats. BMC Compl Alternative Med 2004;4:8. in Google Scholar PubMed PubMed Central

16. Saleem, MN, Idris, M. Podina (Mentha arvensis): transformation from food additive to multifunctional medicine. ARC J Pharmaceut Sci 2016;2:6–15. in Google Scholar

17. Thawkar, BS, Jawarkar, AG, Kalamkar, PV, Pawar, KP, Kale, MK. Phytochemical and pharmacological review of Mentha arvensis. Int J Green Pharm 2016;10:71–6.Search in Google Scholar

18. Ghani, N. Khazain al-Avia. New Delhi: Idara Kitab al-Shifa; 2011:478–80, 202–3, 999–1004 pp.Search in Google Scholar

19. Baitar, I Kitab al-Jame li Mufradat al-Advia wa al-Aghziya. New Delhi: Central Council for Research in Unani Medicine; 2003, vol 1V:397–9, 379–81, 115–7 pp.Search in Google Scholar

20. Ali, AM, Mackeen, MM, El-Sharkawy, SH, Hamid, JA, Ismail, NH, Ahmad, FB, et al.. Antiviral and cytotoxic activities of some plants used in Malaysian indigenous medicine. Pertanika J Trop Agric Sci 1996;19:129–36.Search in Google Scholar

21. Roy, S, Chaurvedi, P, Chowdhary, A. Evaluation of antiviral activity of essential oil of Trachyspermum Ammi against Japanese encephalitis virus. Pharmacogn Res 2015;7:263–7. in Google Scholar

22. Hussein, G, Miyashiro, H, Nakamura, N, Hattori, M, Kakiuchi, N, Shimotohno, K. Inhibitory effects of sudanese medicinal plant extracts on hepatitis C virus (HCV) protease. Phytother Res 2000;14:510–6.<510::aid-ptr646>;2-b.10.1002/1099-1573(200011)14:7<510::AID-PTR646>3.0.CO;2-BSearch in Google Scholar

23. Bairwa, R, Sodha, RS, Rajawat, BS. Trachyspermum ammi. Pharm Rev 2012;6:56–60. in Google Scholar

24. Khan, MR, Jamal, MA, Zeenat, F. Therapeutic potential of Cinnamomum camphora (Kafoor) in skin disorders: a review. World J Pharmaceut Life Sci 2019;5:108–11.Search in Google Scholar

25. Chen, W, Vermaak, I, Viljoen, A. Camphor--a fumigant during the Black Death and a coveted fragrant wood in ancient Egypt and Babylon--a review. Molecules 2013;18:5434–54. in Google Scholar

26. Lee, HJ, Hyun, EA, Yoon, WJ, Kim, BH, Rhee, MH, Kang, HK, et al.. In vitro anti-inflammatory and anti-oxidative effects of Cinnamomum camphora extracts. J Ethnopharmacol 2006;103:208–16. in Google Scholar

27. Tanabe, H, Fukutomi, R, Yasui, K, Kaneko, A, Imai, S, Nakayama, T, et al.. Identification of dimethylmatairesinol as an immunoglobulin E-suppressing component of the leaves of Cinnamomum camphora. J Health Sci 2011;57:184–7. in Google Scholar

28. Pettersen, EF, Goddard, TD, Huang, CC, Couch, GS, Greenblatt, DM, Meng, EC, et al.. UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem 2004;25:1605–12. in Google Scholar

29. Kim, S, Thiessen, PA, Bolton, EE, Chen, J, Fu, G, Gindulyte, A, et al.. PubChem substance and compound databases. Nucleic Acids Res 2016;44:D1202–13. in Google Scholar

30. ChemAxon. MarvinSketch; 2020. Available from: in Google Scholar

31. Trott, O, Olson, AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010;31:455–61. in Google Scholar

32. BIOVIA, Dassault Systèmes, discovery studio visualizer V20.1. San Diego: Dassault Systèmes; 2020. Available from: in Google Scholar

33. Hess, B, Kutzner, C, van der Spoel, D, Lindahl, E. GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theor Comput 2008;4:435–47. in Google Scholar

34. Schüttelkopf, AW, van Aalten, DM. PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr D Biol Crystallogr 2004;60:1355–63. in Google Scholar PubMed

35. Oostenbrink, C, Villa, A, Mark, AE, van Gunsteren, WF. A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6. J Comput Chem 2004;25:1656–76. in Google Scholar PubMed

36. Van Der Spoel, D, Lindahl, E, Hess, B, Groenhof, G, Mark, AE, Berendsen, HJ. GROMACS: fast, flexible, and free. J Comput Chem 2005;26:1701–18. in Google Scholar PubMed

37. Turner, PJ. XMGRACE, version 5.1. 19. Beaverton, OR: Center for Coastal and Land-Margin Research, Oregon Graduate Institute of Science and Technology; 2005.Search in Google Scholar

38. Kumari, R, Kumar, R, Open Source Drug Discovery Consortium, Lynn, A. g_mmpbsa--a GROMACS tool for high-throughput MM-PBSA calculations. J Chem Inf Model 2014;54:1951–62. in Google Scholar PubMed

39. Jin, Z, Du, X, Xu, Y, Deng, Y, Liu, M, Zhao, Y, et al.. Structure of M pro from SARS-CoV-2 and discovery of its inhibitors. Nature 2020;582:289–93. in Google Scholar PubMed

40. Naik, B, Gupta, N, Ojha, R, Singh, S, Prajapati, VK, Prusty, D. High throughput virtual screening reveals SARS-CoV-2 multi-target binding natural compounds to lead instant therapy for COVID-19 treatment. Int J Biol Macromol 2020;160:1–17. in Google Scholar PubMed PubMed Central

41. Gao, LQ, Xu, J, Chen, SD. In silico screening of potential Chinese herbal medicine against COVID-19 by targeting SARS-CoV-2 3CLpro and angiotensin converting enzyme II using molecular docking. Chin J Integr Med 2020;26:527–32. in Google Scholar PubMed PubMed Central

42. Tahir Ul Qamar, M, Alqahtani, SM, Alamri, MA, Chen, LL. Structural basis of SARS-CoV-2 3CL pro and anti-COVID-19 drug discovery from medicinal plants. J Pharm Anal 2020;10:313–9. in Google Scholar PubMed PubMed Central

43. Athira Nair, D, James, TJ. Computational screening of phytocompounds from Moringa oleifera leaf as potential inhibitors of SARS-CoV-2 Mpro. Res Square 2020. in Google Scholar

44. Biswas, NN, Saha, S, Ali, MK. Antioxidant, antimicrobial, cytotoxic and analgesic activities of ethanolic extract of Mentha arvensis L. Asian Pac J Trop Biomed 2014;4:792–7. in Google Scholar

45. Li, Y, Yao, J, Han, C, Yang, J, Chaudhry, MT, Wang, S, et al.. Quercetin, inflammation and immunity. Nutrients 2016;8:167. in Google Scholar PubMed PubMed Central

46. Wu, W, Li, R, Li, X, He, J, Jiang, S, Liu, S, et al.. Quercetin as an antiviral agent inhibits influenza A virus (IAV) entry. Viruses 2015;8:6. in Google Scholar PubMed PubMed Central

47. Pandit, M, Latha, N. In silico studies reveal potential antiviral activity of phytochemicals from medicinal plants for the treatment of COVID-19 infection. Res Square 2020. in Google Scholar

Supplementary Material

The online version of this article offers supplementary material (

Received: 2021-06-05
Accepted: 2021-10-06
Published Online: 2021-10-22

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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