Antiviral Chlorinated\nDrimane Meroterpenoids from\nthe Fungus <i>Talaromyces pinophilus</i> LD‑7 and\nTheir Biosynthetic Pathway

Ten new drimane meroterpenoids talarines A–J (<b>1</b>–<b>10</b>), along with six known analogues <b>(11–16)</b>, were isolated from desert soil-derived fungus Talaromyces\npinophilus LD-7. Their 2D structures were elucidated\nby comprehensive interpretation of NMR and HRESIMS data. Electronic\ncircular dichroism calculation was used to establish their absolute\nconfigurations. Compounds <b>2</b>, <b>10</b>, and <b>11</b> showed antiviral activities toward vesicular stomatitis\nvirus with IC<sub>50</sub> values of 18, 15, and 23 nM, respectively.\nThe structure-bioactivity relationship indicated that chlorine substitution\nat C-5 contributed greatly to their antiviral activities. Finally,\nwe identified a new halogenase outside the biosynthetic gene cluster,\nwhich was responsible for C-5 halogenation of the precursor isocoumarin <b>17</b> as a tailoring step in chlorinated meroterpenoids assembly.