HIV

The nucleoside derivatives found in Cordyceps species, including cordycepin (3’-deoxyadenosine), are reverse transcriptase inhibitors of the type now being used to treat HIV and in vitro studies confirm their efficacy in inhibiting HIV replication1-3. PSK and PSP from Trametes versicolor have also been shown to inhibit both HIV-1 reverse transcriptase and protease, two key enzymes in the life cycle of HIV4-6, as have triterpenes from Ganoderma lucidum, which also inhibit NF-kappaB expression and viral binding7,8.

There is in vitro evidence that betulinic acid analogues (present in Inonotus obliquus) disrupt HIV fusion to the cell membrane in a post-binding step through interaction with the viral glycoprotein gp41 as well as disrupting assembly and budding of the HIV-1 virus9,10, while proteins from Flammulina velutipes have been shown to inhibit HIV-1 reverse transcriptase, beta-glucosidase and beta-glucuronidase.

T. versicolor mycelial biomass supplementation (3g/day) given as part of traditional Chinese medicine treatment for patients with HIV produced improvements in CD4 count and reductions in viral load as well as fading of Kaposi’s sarcoma (caused by human herpes virus 8) in AIDS patients11,12.

CLINICAL NOTE
C. militaris shows particular promise in the treatment of HIV and other viral conditions, especially in combination with mushroom polysaccharide extracts.

REFERENCES
1. Emerging antiviral drugs from medicinal mushrooms. Pirano FF. Int J Med Mushrooms. 2006;8(2):101–114.
2. Phosphorothioate and cordycepin analogues of 2’, 5’- oligoadenylate: Inhibition of Human Immunodeficiency Virus type 1 reverse transcriptase and infection in vitro. Montefiori DC, Sobol RW Jr, Li SW, Reichenbach NL, Suhadolnik RJ, Charubala R, Pfleiderer W, Modliszewski A, Robinson WE Jr, Mitchell WM. Proc Natl Acad Sci USA. 1989;86(18):7191–7194.
3. Synthesis, characterization, and biological activity of monomeric and trimeric cordycepin-cholesterol conjugates and inhibition of HIV-1 replication. Wasner M, Henderson EE, Suhadolnik RJ, Pfleiderer W. Helv Chim Acta. 1994;77(7):1757–1761.
4. Polysaccharopeptide from the Turkey tail fungus Trametes versicolor (L.:Fr.) Pilát inhibits Human Immunodeficiency Virus type 1 reverse transciptase and protease. Ng TB, Wang HX, Wan DCC. Int J Med Mushrooms. 2006;8(1):39–43.
5. Polysaccharopeptide from Coriolus versicolor has potential for use against Human Immunodeficiency Virus type 1 infection. Collins RA, Ng TB. Life Sci. 1997;60(25):383–387.
6. A biological response modifier, PSK, inhibits reverse transcriptase in vitro. Hirose K, Hakozaki M, Kakuchi J, Matsunaga K, Yoshikumi C, Takahashi M, Tochikura TS, Yamamoto N. Biochem Biophys Res Commun. 1987;149(2):562–567.
7. Anti-HIV-1 and anti-HIV-1-protease substances from Ganoderma lucidum. el-Mekkawy S, Meselhy MR, Nakamura N, Tezuka Y, Hattori M, Kakiuchi N, Shimotohno K, Kawahata T, Otake T. Phytochemistry. 1998;49(6):1651–1657.
8. Triterpenes from the spores of Ganoderma lucidum and their inhibitory activity against HIV-1 protease. Min BS, Nakamura N, Miyashiro H, Bae KW, Hattori M. Chem Pharm Bull. 1998;46(10):1607–1612.
9. Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. Cichewicz RH, Kouzi SA. Med Res Rev. 2004;24(1):90–114.
10. Betulinic acid derivatives as Human Immunodeficiency Virus type 2 (HIV-2) inhibitors. Dang Z, Lai W, Qian K, Ho P, Lee KH, Chen CH, Huang L. J Med Chem. 2009;52(23):7887–7891.
11. The effectiveness of Coriolus versicolor supplementation in the treatment of Kaposi sarcoma in HIV+Patients. [Poster]. Tindall J, Clegg E. Presented at the 10th International Congress of Mucosal Immunology in Amsterdam, June 28th – July 1st, 1999.
12. The clinical use of Coriolus versicolor supplementation in HIV+ patients and the impact on CD4 count and viral load. [Poster]. Pfeiffer M. Presented at the III International Symposium on Mushroom Nutrition in Milan on Saturday, March 10th, 2001.