A Study to Assess the Safety, Pharmacokinetics, and Antiviral Activity of ABI-5366 in Healthy Participants and Participants Seropositive for HSV-2 With Recurrent Genital Herpes

• ABI-5366 (Drug): Once daily tablet dosing (SAD) or weekly or monthly tablet dosing over the 29-day treatment period (MAD)
• ABI-5366 Placebo (Drug): Once daily tablet dosing (SAD) or weekly or monthly tablet dosing over the 29-day treatment period (MAD)

Primary outcomes

• Area Under the Plasma Concentration Time Curve (AUC) of ABI-5366 [SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.]
• Maximum Observed Plasma Concentration (Cmax) of ABI-5366 [SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.]
• Time to Cmax (Tmax) of ABI-5366 [SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.]
• Apparent Terminal Elimination Half Life (t 1/2) of ABI-5366 [SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.]
• Apparent Systemic Clearance (CL/F) of ABI-5366 [SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.]
• Apparent Volume of Distribution (Vz/F) of ABI-5366 [SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.]
• Dose normalized AUCs and Cmax of ABI-5366 [SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.]
• Proportion of subjects with adverse events (AEs), premature treatment discontinuation due to AEs, and abnormal laboratory results [Up to 98 days after last dose]

Secondary outcomes

• SAD Cohorts: Comparison of plasma AUC and Cmax between fasted and fed treatments [SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing.]
• MAD Cohorts: If applicable, comparison of plasma PK profiles and parameters with and without loading doses [MAD Cohorts: At pre-specified time points from Days 8 to 36.]
• MAD Cohorts: Difference in viral shedding rate (number of anogenital swabs positive for HSV-2 DNA/total number of swabs) across treatments [MAD Cohorts: At pre-specified time points from Days 8 to 36.]
• MAD Cohorts: Difference in mean and median HSV-2 DNA copies/mL for swab samples positive for HSV-2 DNA across treatments [MAD Cohorts: At pre-specified time points from Days 8 to 36.]
• MAD Cohorts: Difference in the proportion of swab samples with HSV-2 DNA >4 log10 copies/mL across treatments (number of swabbing samples with HSV-2 DNA >4 log10 copies/mL / total number of swabs obtained) [MAD Cohorts: At pre-specified time points from Days 8 to 36.]
• MAD Cohorts: Difference in number of shedding episodes during the swabbing period across treatments [MAD Cohorts: At pre-specified time points from Days 8 to 36.]
• MAD Cohorts: Difference in duration of shedding episodes during the swabbing period across treatments [MAD Cohorts: At pre-specified time points from Days 8 to 36.]
• MAD Cohorts: Difference in subclinical shedding rate (number of swabs positive for HSV-2 DNA in the absence of lesions/total number of swabs in the absence of lesions) across treatments [MAD Cohorts: At pre-specified time points from Days 8 to 36.]
• MAD Cohorts: Difference in lesion rate during the swabbing period across treatments [MAD Cohorts: At pre-specified time points from Days 8 to 36.]
• MAD Cohorts: Difference in lesion duration during the swabbing period across treatments [MAD Cohorts: At pre-specified time points from Days 8 to 36.]
• MAD Cohorts: Difference in recurrence rate (number of reappearances of lesions during the swabbing period/total days assessed) across treatments [MAD Cohorts: At pre-specified time points from Days 8 to 36.]

Sex: All, ages: 18 Years to 60 Years, accepts healthy volunteers

Part A: Inclusion Criteria:

* Subject has a body mass index (BMI) between ≥ 18.0 and < 32.0 kg/m2
* In good health (as determined by the Investigator) based on medical history, physical examination, ECG, and clinical laboratory results.
* Female subjects must be non-pregnant and have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day -1 or Day 1 (predose)
* Agreement to comply with protocol-specified contraceptive requirements

Part B: Inclusion Criteria:

* Subject has a body mass index (BMI) between ≥ 18.0 and < 32.0 kg/m2
* Other than HSV infection, is in good health (as determined by the Investigator) based on medical history, physical examination, ECG, and clinical laboratory results.
* Female subjects must be non-pregnant and have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1 (predose)
* Agreement to comply with protocol-specified contraceptive requirements

Part A and B: Exclusion Criteria:

* Current infection of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), acute hepatitis A virus (HAV), or acute hepatitis E virus (HEV).
* History of any illness that, in the opinion of the Investigator, might confound the results of the study, pose an additional risk in administering study drug to the subject, or a condition known to interfere with the absorption/distribution/elimination of drugs.
* History of any significant drug-related allergic reactions such as anaphylaxis, Stevens-Johnson syndrome, urticaria, or multiple drug allergies
* History of persistent alcohol abuse or illicit drug abuse within 3 years prior to Screening
* Has participated in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 half-lives before Screening, whichever is longer.