2016, Craun Research announced the successful completion of Phase I trial of the drug. In 2019, Dr Annuar Rapaee, Sarawak Assistant Minister for Education, Science and Technological Research admitted the slow progress in developing and commercialising the drug. Types and derivatives Since the discovery of Calanolide A, other similar calanolides have been described (from Calanolide B to Calanolide F). All these compounds are derived naturally from the Calophyllum species of plants. Besides, other plants are found to produce Calanolide A other than Calophyllum lanigerum var. austrocoriaceum. These are: Calophyllum brasiliense, Calophyllum inophyllum, Calophyllum teysmannii, and Clausena excavata. Calanolide A exists in the form of oil in its natural physical state. There are several structure–activity relationships that give Calanolide A its desired anti-HIV activity. A very specific stereochemistry and optical rotation is required for its anti-HIV activity. Besides, racemic mixture of Calanolide A with its enantiomer (±)-12-oxocalanolide A is more active than Calanolide A alone. A C-12 heteroatom is also needed for the activity while medication of C-4 can affect its anti-HIV properties. Hydrogenation of C-7 and C-8 has little effect on its activity. In 2017, F18, a structural analog of Calanolide A could have more potent anti-HIV activity than original molecule. Biosynthesis The biosynthesis of Calanolide A in plants is not completely understood. The Calanolide A is synthesised from a precursor molecule L-phenylalanine. The precursor molecule then is converted into umbelliferone. After that, the umbelliferone molecule go through two pathways: either being converted into 5,7-dihydroxycoumarin or osthenol before being converted into dipetalolactone (a pyranocoumarin). Dipetalolactone is then converted into 3-propyl-intermediate. Through Wagner–Meerwein rearrangement reaction, the propyl intermediate is converted into Calanolide A, B, or C with the help of p450 monooxygenase enzyme. Pharmacodynamics The drug has half-life of 20 hours. The drug is metabolised by cytochrome P450 CYP3A. Mechanism of action Calanolide A is unique among non-nucleoside reverse transcriptase inhibitor (NNRTIs) in that it can bind to two distinct sites on HIV reverse transcriptase enzyme. It may either bind to one or another site in the reverse transcriptase, but not both sites at the same time. The two sites are active site (binding site for 1-ethoxymethyl-5-ethyl-6-phenylthio-2-thiouracil) and Foscarnet (also known as phosphonoformic acid) binding site of the reverse transcriptase enzyme. The drug also acts synergistically with nevirapine in inhibiting HIV-1 virus. Besides, Calanolide A is also a partially competitive inhibitor of dNTP (deoxyribonucleotide triphosphate) binding site of the enzyme. However,