Breviane Spiroditerpenoids\nwith Anti-inflammatory\nand Antiviral Activities from Deep-Sea-Derived Fungus <i>Penicillium</i> sp. F59

Twelve\nnew breviane spiroditerpenoids, namely, chrysobreviones\nA–L (<b>1</b>–<b>12</b>), together with\nseven structurally related analogues (<b>13</b>–<b>19</b>) were isolated from the EtOAc extract of the fermented\ncultures of deep-sea-derived fungus <i>Penicillium</i> sp.\nF59. These structures including absolute configurations were resolved\non the basis of extensive analysis of NMR spectroscopic data and HRESIMS,\nin association with experimental and calculated ECD data as well as\nthe modified Mosher’s method. Compound <b>1</b> represented\nthe first breviane derivative containing an unusual octahydrodifuro[2,3-b:2′,3′-d]furan\nmoiety, while <b>7</b> and <b>9</b> were the first breviones\nfeaturing an epoxy ring and an 18-hydroxymethyl group, respectively.\nThe anti-inflammatory and antiviral activities of compounds <b>1</b>–<b>19</b> were evaluated. Compounds <b>1</b>, <b>8</b>, <b>16</b>, and <b>17</b> showed inhibitory\neffects against NO secretion in LPS-activated Raw264.7 macrophage\ncells with IC<sub>50</sub> values ranging from 1.4 to 12.9 μM,\nwhile <b>1</b> and <b>7</b> exhibited antiviral effects\nagainst severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)\nomicron subvariant BA.2 pseudovirus with IC<sub>50</sub> values of\n8.5 and 10.3 μM, respectively.