Exploration of Drug Science

Table 1. Computed physicochemical properties of Hz-A and Hz-B

Products	Hz-A	Hz-B
Molecular weight	268.3	314.3
Dipole moment (D)	2.9	2.8
Total solvent accessible surface area (SASA; Å²)^*	525.3	552.2
Hydrophobic SASA	290.3	247.5
Hydrophilic SASA	224.8	294.5
Molecular volume (Å³)	911.0	978.2
H-bond donor	2	4
H-bonds acceptor	5	7
log P (octanol/water)	1.9	1.8
log S (aqueous solubility)	–2.9	–2.7

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^* SASA calculated with a radius probe of 1.4 Å. Drug properties were calculated with the Biochemical and Organic Simulation System (BOSS) 4.9 software. Partition coefficient (log P)

Declarations

Author contributions

GV: Visualization, Software, Data curation. CB: Conceptualization, Investigation, Visualization, Writing—original draft, Writing—review & editing.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

All relevant data is contained within the manuscript.

Funding

Not applicable.

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References

Abdenaceur R, Farida BT, Mourad D, Rima H, Zahia O, Fatma SH. Effective biofertilizer Trichoderma spp. isolates with enzymatic activity and metabolites enhancing plant growth. Int Microbiol. 2022;25:817–29. [DOI] [PubMed]

Abdelmoaty S, Khandaker MM, Mahmud K, Majrashi A, Alenazi MM, Badaluddin NA. Influence of Trichoderma harzianum and Bacillus thuringiensis with reducing rates of NPK on growth, physiology, and fruit quality of Citrus aurantifolia. Braz J Biol. 2022;82:e261032. [DOI] [PubMed]

Hao D, Lang B, Wang Y, Wang X, Liu T, Chen J. Designing synthetic consortia of Trichoderma strains that improve antagonistic activities against pathogens and cucumber seedling growth. Microb Cell Fact. 2022;21:234. [DOI] [PubMed] [PMC]

Zhang H, Kong N, Liu B, Yang Y, Li C, Qi J, et al. Biocontrol potential of Trichoderma harzianum CGMCC20739 (Tha739) against postharvest bitter rot of apples. Microbiol Res. 2022;265:127182. [DOI] [PubMed]

Liu L, Xu Y, Cao H, Fan Y, Du K, Bu X, et al. Effects of Trichoderma harzianum biofertilizer on growth, yield, and quality of Bupleurum chinense. Plant Direct. 2022;6:e461. [DOI] [PubMed] [PMC]

Rahman M, Borah SM, Borah PK, Bora P, Sarmah BK, Lal MK, et al. Deciphering the antimicrobial activity of multifaceted rhizospheric biocontrol agents of solanaceous crops viz., Trichoderma harzianum MC2, and Trichoderma harzianum NBG. Front Plant Sci. 2023;14:1141506. [DOI] [PubMed] [PMC]

Caccavo V, Forlano P, Mang SM, Fanti P, Nuzzaci M, Battaglia D, et al. Effects of Trichoderma harzianum strain T22 on the arthropod community associated with tomato plants and on the crop performance in an experimental field. Insects. 2022;13:418. [DOI] [PubMed] [PMC]

Mukherjee A, Ghosh SK. An eco-friendly approach of biocontrol of aphid (Aphis gossypii Glover) by Trichoderma harzianum. Environ Monit Assess. 2022;195:102. [DOI] [PubMed]

Dhaver P, Pletschke B, Sithole B, Govinden R. Isolation, screening, preliminary optimisation and characterisation of thermostable xylanase production under submerged fermentation by fungi in Durban, South Africa. Mycology. 2022;13:271–92. [DOI] [PubMed] [PMC]

10.

Konappa N, Udayashankar AC, Dhamodaran N, Krishnamurthy S, Jagannath S, Uzma F, et al. Ameliorated antibacterial and antioxidant properties by Trichoderma harzianum mediated green synthesis of silver nanoparticles. Biomolecules. 2021;11:535. [DOI] [PubMed] [PMC]

11.

Guarro J, Antolín-Ayala MI, Gené J, Gutiérrez-Calzada J, Nieves-Díez C, Ortoneda M. Fatal case of Trichoderma harzianum infection in a renal transplant recipient. J Clin Microbiol. 1999;37:3751–5. [DOI] [PubMed] [PMC]

12.

Kantarcioğlu AS, Celkan T, Yücel A, Mikami Y, Kurugoglu S, Mitani H, et al. Fatal Trichoderma harzianum infection in a leukemic pediatric patient. Med Mycol. 2009;47:207–15. [DOI] [PubMed]

13.

Nuansri S, Rukachaisirikul V, Rungwirain N, Kaewin S, Yimnual C, Phongpaichit S, et al. α-Pyrone and decalin derivatives from the marine-derived fungus Trichoderma harzianum PSU-MF79. Nat Prod Res. 2022;36:5462–9. [DOI] [PubMed]

14.

Liu Z, Sun Y, Tang M, Sun P, Wang A, Hao Y, et al. Trichodestruxins A–D: cytotoxic cyclodepsipeptides from the endophytic fungus Trichoderma harzianum. J Nat Prod. 2020;83:3635–41. [DOI] [PubMed]

15.

Zhu F, Zhao X, Li J, Guo L, Bai L, Qi X. A new compound Trichomicin exerts antitumor activity through STAT3 signaling inhibition. Biomed Pharmacother. 2020;121:109608. [DOI] [PubMed]

16.

Chen Y, Zhuang Z, Yang J, Bai L. Screening of microbial natural products and biological evaluation of Trichomicin as potential anti-cytokine storm agents. Front Pharmacol. 2021;12:770910. [DOI] [PubMed] [PMC]

17.

Jeerapong C, Phupong W, Bangrak P, Intana W, Tuchinda P. Trichoharzianol, a new antifungal from Trichoderma harzianum F031. J Agric Food Chem. 2015;63:3704–8. [DOI] [PubMed]

18.

Yamada T, Suzue M, Arai T, Kikuchi T, Tanaka R. Trichodermanins C–E, new diterpenes with a fused 6-5-6-6 ring system produced by a marine sponge-derived fungus. Mar Drugs. 2017;15:169. [DOI] [PubMed] [PMC]

19.

Yamada T, Fujii A, Kikuchi T. New diterpenes with a fused 6-5-6-6 ring system isolated from the marine sponge-derived fungus Trichoderma harzianum. Mar Drugs. 2019;17:480. [DOI] [PubMed] [PMC]

20.

Hanson JR. The chemistry of the bio-control agent, Trichoderma harzianum. Sci Prog. 2005;88:237–48. [DOI] [PubMed] [PMC]

21.

Guo R, Li G, Zhang Z, Peng X. Structures and biological activities of secondary metabolites from Trichoderma harzianum. Mar Drugs. 2022;20:701. [DOI] [PubMed] [PMC]

22.

Li B, Li L, Peng Z, Liu D, Si L, Wang J, et al. Harzianoic acids A and B, new natural scaffolds with inhibitory effects against hepatitis C virus. Bioorg Med Chem. 2019;27:560–7. [DOI] [PubMed]

23.

New C, Lee ZY, Tan KS, Wong AH, Wang Y, Tran T. Tetraspanins: host factors in viral infections. Int J Mol Sci. 2021;22:11609. [DOI] [PubMed] [PMC]

24.

Florin L, Lang T. Tetraspanin assemblies in virus infection. Front Immunol. 2018;9:1140. [DOI] [PubMed] [PMC]

25.

Benayas B, Sastre I, López-Martín S, Oo A, Kim B, Bullido MJ, et al. Tetraspanin CD81 regulates HSV-1 infection. Med Microbiol Immunol. 2020;209:489–98. [DOI] [PubMed] [PMC]

26.

Lasswitz L, Zapatero-Belinchón FJ, Moeller R, Hülskötter K, Laurent T, Carlson LA, et al. The tetraspanin CD81 is a host factor for chikungunya virus replication. mBio. 2022;13:e00731-22. [DOI] [PubMed] [PMC]

27.

Titu S, Grapa CM, Mocan T, Balacescu O, Irimie A. Tetraspanins: physiology, colorectal cancer development, and nanomediated applications. Cancers (Basel). 2021;13:5662. [DOI] [PubMed] [PMC]

28.

Deng Y, Cai S, Shen J, Peng H. Tetraspanins: novel molecular regulators of gastric cancer. Front Oncol. 2021;11:702510. [DOI] [PubMed] [PMC]

29.

Floren M, Gillette JM. Acute myeloid leukemia: therapy resistance and a potential role for tetraspanin membrane scaffolds. Int J Biochem Cell Biol. 2021;137:106029. [DOI] [PubMed] [PMC]

30.

Vences-Catalán F, Rajapaksa R, Kuo CC, Miller CL, Lee A, Ramani VC, et al. Targeting the tetraspanin CD81 reduces cancer invasion and metastasis. Proc Natl Acad Sci USA. 2021;118:e2018961118. [DOI] [PubMed] [PMC]

31.

Anand K, Khan FI, Singh T, Elumalai P, Balakumar C, Premnath D, et al. Green synthesis, experimental and theoretical studies to discover novel binders of exosomal tetraspanin CD81 protein. ACS Omega. 2020;5:17973–82. [DOI] [PubMed] [PMC]

32.

Bailly C, Thuru X. Targeting of tetraspanin CD81 with monoclonal antibodies and small molecules to combat cancers and viral diseases: an overview. Cancers. 2023;15:2186. [DOI] [PubMed] [PMC]

33.

Yang Y, Liu XR, Greenberg ZJ, Zhou F, He P, Fan L, et al. Open conformation of tetraspanins shapes interaction partner networks on cell membranes. EMBO J. 2020;39:e105246. [DOI] [PubMed] [PMC]

34.

Palor M, Stejskal L, Mandal P, Lenman A, Alberione MP, Kirui J, et al. Cholesterol sensing by CD81 is important for hepatitis C virus entry. J Biol Chem. 2020;295:16931–48. [DOI] [PubMed] [PMC]

35.

Zimmerman B, Kelly B, McMillan BJ, Seegar TCM, Dror RO, Kruse AC, et al. Crystal structure of a full-length human tetraspanin reveals a cholesterol-binding pocket. Cell. 2016;167:1041–51.E11. [DOI] [PubMed] [PMC]

36.

Cunha ES, Sfriso P, Rojas AL, Roversi P, Hospital A, Orozco M, et al. Mechanism of structural tuning of the hepatitis C virus human cellular receptor CD81 large extracellular loop. Structure. 2017;25:53–65. Erratum in: Structure. 2018;26:181. [DOI] [PubMed]

37.

Tian W, Chen C, Lei X, Zhao J, Liang J. CASTp 3.0: computed atlas of surface topography of proteins. Nucleic Acids Res. 2018; 46:W363–7. [DOI] [PubMed] [PMC]

38.

Jorgensen WL, Tirado-Rives J. Monte Carlo vs molecular dynamics for conformational sampling. J Phys Chem. 1996;100:14508–13. [DOI]

39.

Jorgensen WL, Tirado-Rives J. Molecular modeling of organic and biomolecular systems using BOSS and MCPRO. J Comput Chem. 2005;26:1689–700. [DOI] [PubMed]

40.

Jorgensen WL, Ulmschneider JP, Tirado-Rives J. Free energies of hydration from a generalized born model and an ALL-atom force field. J Phys Chem B. 2004;108:16264–70. [DOI]

41.

Jones G, Willett P, Glen RC, Leach AR, Taylor R. Development and validation of a genetic algorithm for flexible docking. J Mol Biol. 1997;267:727–48. [DOI] [PubMed]

42.

Meziane-Tani M, Lagant P, Semmoud A, Vergoten G. The SPASIBA force field for chondroitin sulfate: vibrational analysis of _D-glucuronic and N-acetyl-_D-galactosamine 4-sulfate sodium salts. J Phys Chem A. 2006;110:11359–70. [DOI] [PubMed]

43.

Vergoten G, Mazur I, Lagant P, Michalski JC, Zanetta JP. The SPASIBA force field as an essential tool for studying the structure and dynamics of saccharides. Biochimie. 2003;85:65–73. [DOI] [PubMed]

44.

Lagant P, Nolde D, Stote R, Vergoten G, Karplus M. Increasing normal modes analysis accuracy: the SPASIBA spectroscopic force field introduced into the CHARMM program. J Phys Chem A. 2004;108:4019–29. [DOI]

45.

Homans SW. A molecular mechanical force field for the conformational analysis of oligosaccharides: comparison of theoretical and crystal structures of Man alpha 1-3Man beta 1-4GlcNAc. Biochemistry. 1990;29:9110–8. [DOI] [PubMed]

46.

Hochheimer N, Sies R, Aschenbrenner AC, Schneider D, Lang T. Classes of non-conventional tetraspanins defined by alternative splicing. Sci Rep. 2019;9:14075. [DOI] [PubMed] [PMC]

47.

Lang T, Hochheimer N. Tetraspanins. Curr Biol. 2020;30:R204–6. [DOI] [PubMed]

48.

Koh HM, Jang BG, Lee DH, Hyun CL. Increased CD9 expression predicts favorable prognosis in human cancers: a systematic review and meta-analysis. Cancer Cell Int. 2021;21:472. [DOI] [PubMed] [PMC]

49.

Zeng P, Si M, Sun RX, Cheng X, Li XY, Chen MB. Prognostic value of CD9 in solid tumor: a systematic review and meta-analysis. Front Oncol. 2021;11:764630. [DOI] [PubMed] [PMC]

50.

Suhasini PC, Shetty SS, Nalilu SK, Shetty PK, Patil P. Tetraspanin CD9: a friend or foe of head and neck cancer (review). Oncol Rep. 2022;47:88. [DOI] [PubMed] [PMC]

51.

Lorico A, Lorico-Rappa M, Karbanová J, Corbeil D, Pizzorno G. CD9, a tetraspanin target for cancer therapy? Exp Biol Med (Maywood). 2021;246:1121–38. [DOI] [PubMed] [PMC]

52.

Umeda R, Satouh Y, Takemoto M, Nakada-Nakura Y, Liu K, Yokoyama T, et al. Structural insights into tetraspanin CD9 function. Nat Commun. 2020;11:1606. [DOI] [PubMed] [PMC]

53.

Oosterheert W, Xenaki KT, Neviani V, Pos W, Doulkeridou S, Manshande J, et al. Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-F. Life Sci Alliance. 2020;3:e202000883. [DOI] [PubMed] [PMC]

54.

Umeda R, Nishizawa T, Nureki O. Crystallization of the human tetraspanin protein CD9. Acta Crystallogr. F Struct Biol Commun. 2019;75:254–9. [DOI] [PubMed] [PMC]

55.

Rydland A, Heinicke F, Flåm ST, Mjaavatten MD, Lie BA. Small extracellular vesicles have distinct CD81 and CD9 tetraspanin expression profiles in plasma from rheumatoid arthritis patients. Clin Exp Med. 2023;23:2867–75. [DOI] [PubMed] [PMC]

56.

Zuppone S, Zarovni N, Vago R. The cell type dependent sorting of CD9- and CD81 to extracellular vesicles can be exploited to convey tumor sensitive cargo to target cells. Drug Deliv. 2023;30:2162161. [DOI] [PubMed] [PMC]

57.

Zainul R, Yanuarti E, Amiroch S, Albari MT, Verawati R, Lubis AP, et al. Interaction of masilinic acid from clove plant (Syzygium aromaticum) with CD81 antigen in inhibiting HIV virus regulation in silico. Pharmacogn J. 2023;15:484–8. [DOI]

58.

Dey D, Biswas P, Paul P, Mahmud S, Ema TI, Khan AA, et al. Natural flavonoids effectively block the CD81 receptor of hepatocytes and inhibit HCV infection: a computational drug development approach. Mol Divers. 2022;27:1309–22. [DOI] [PubMed]

59.

Zheljazkov VD, Cantrell CL, Jeliazkova EA, Astatkie T, Schlegel V. Essential oil yield, composition, and bioactivity of Sagebrush species in the Bighorn mountains. Plants (Basel). 2022;11:1228. [DOI] [PubMed] [PMC]

60.

Bader A, AlQathama A, Cioni PL, Ceccarini L, Abdelhady MIS, Al-Shareef W, et al. Essential oil biodiversity of Achillea ligustica All. Obtained from Mainland and Island populations. Plants (Basel). 2022;11:1054. [DOI] [PubMed] [PMC]

61.

Chen J, Shi Z, Li C, Lu P. Catalytic enantioselective synthesis of benzocyclobutenols and cyclobutanols via a sequential reduction/C–H functionalization. Chem Sci. 2021;12:10598–604. [DOI] [PubMed] [PMC]

62.

Radulović NS, Dekić MS, Ranđelović PJ, Stojanović NM, Zarubica AR, Stojanović-Radić ZZ. Toxic essential oils: anxiolytic, antinociceptive and antimicrobial properties of the yarrow Achillea umbellata Sibth. et Sm. (Asteraceae) volatiles. Food Chem Toxicol. 2012;50:2016–26. [DOI] [PubMed]

63.

Ambrogi BG, Cortés AM, Zarbin PH. Identification of male-produced aggregation pheromone of the curculionid beetle Sternechus subsignatus. J Chem Ecol. 2012;38:272–7. [DOI] [PubMed]

64.

Rahmani R, Wallin EA, Viklund L, Schroeder M, Hedenström E. Identification and field assay of two aggregation pheromone components emitted by males of the bark beetle Polygraphus punctifrons (Coleoptera: Curculionidae). J Chem Ecol. 2019;45:356–65. [DOI] [PubMed] [PMC]

65.

Poplata S, Bach T. Enantioselective intermolecular [2+2] photocycloaddition reaction of cyclic enones and its application in a synthesis of (−)-grandisol. J Am Chem Soc. 2018;140:3228–31. [DOI] [PubMed] [PMC]

66.

Hari DP, Abell JC, Fasano V, Aggarwal VK. Ring-expansion induced 1,2-metalate rearrangements: highly diastereoselective synthesis of cyclobutyl boronic esters. J Am Chem Soc. 2020;142:5515–20. [DOI]

67.

Küppers R. CD81 as target for B cell lymphomas. J Exp Med. 2019;216:1469–70. [DOI] [PubMed] [PMC]

68.

Nelson B, Adams J, Kuglstatter A, Li Z, Harris SF, Liu Y, et al. Structure-guided combinatorial engineering facilitates affinity and specificity optimization of anti-CD81 antibodies. J Mol Biol. 2018;430:2139–52. [DOI] [PubMed]

69.

Vences-Catalán F, Rajapaksa R, Srivastava MK, Marabelle A, Kuo CC, Levy R, et al. Tetraspanin CD81, a modulator of immune suppression in cancer and metastasis. Oncoimmunology. 2015;5:e1120399. [DOI] [PubMed] [PMC]

70.

Ströh LJ, Nagarathinam K, Krey T. Conformational flexibility in the CD81-binding site of the hepatitis C virus glycoprotein E2. Front Immunol. 2018;9:1396. [DOI] [PubMed] [PMC]