Aphidicolin, a tetracyclic diterpenoid, is an antibiotic with novel structure produced by the mold Cephalosporium aphidicola. Aphidicolin is an inhibitor of DNA polymerase-α [1].

DNA polymerase-α is an enzyme complex involved in initiation of DNA replication and during synthesis of Okazaki fragments on the lagging strand. The DNA polymerase-α complex consists of 4 subunits: POLA1, POLA2, PRIM1, and PRIM2. POLA1 is the catalytic subunit. POLA2 is the regulatory subunit. PRIM1 and PRIM2 are the small and the large primase subunits [2].

Aphidicolin selectively inhibited the activity of DNA polymerase-α without activity for DNA polymerase-β and mitochondrial DNA polymerase. Aphidicolin prevented cell division in sea urchin embryos [1]. Aphidicolin was a potent inhibitor of cellular deoxyribonucleic acid synthesis. Aphidicolin strongly inhibited the growth of herpes simplex virus both in tissue culture and in the rabbit eye. Aphidicolin was active against iododeoxyuridine-resistant herpes virus [3]. Aphidicolin showed antiviral activity and inhibited the incorporation of thymidine into DNA of cultured human embryonic lung cells. Aphidicolin (15 μg/ml) reduced the activity of crude and partially purified DNA polymerases from the cytosol [4].

References:
[1] Ikegami S, TAGUCHI T, OHASHI M, et al. Aphidicolin prevents mitotic cell division by interfering with the activity of DNA polymerase-α[J]. Nature, 1978, 275(5679): 458-460.
[2] Lehman I R, Kaguni L S, Krause K H, et al. DNA polymerase alpha[J]. J. Biol. Chem, 1989, 264.
[3] Bucknall R A, Moores H, Simms R, et al. Antiviral effects of aphidicolin, a new antibiotic produced by Cephalosporium aphidicola[J]. Antimicrobial agents and chemotherapy, 1973, 4(3): 294-298.
[4] Ohashi M, Taguchi T, Ikegami S. Aphidicolin: a specific inhibitor of DNA polymerases in the cytosol of rat liver[J]. Biochemical and biophysical research communications, 1978, 82(4): 1084-1090.