Antiviral potential of garlic (Allium sativum) and its organosulfur compounds: A systematic update of pre-clinical and clinical data

Abstract

Background: Garlic (Allium sativum L.) is a common herb consumed worldwide as functional food and traditional remedy for the prevention of infectious diseases since ancient time. Garlic and its active organosulfur compounds (OSCs) have been reported to alleviate a number of viral infections in pre-clinical and clinical investigations. However, so far no systematic review on its antiviral effects and the underlying molecular mechanisms exists.

Scope and approach: The aim of this review is to systematically summarize pre-clinical and clinical investigations on antiviral effects of garlic and its OSCs as well as to further analyse recent findings on the mechanisms that underpin these antiviral actions. PubMed, Cochrane library, Google Scholar and Science Direct databases were searched and articles up to June 2020 were included in this review.

Key findings and conclusions: Pre-clinical data demonstrated that garlic and its OSCs have potential antiviral activity against different human, animal and plant pathogenic viruses through blocking viral entry into host cells, inhibiting viral RNA polymerase, reverse transcriptase, DNA synthesis and immediate-early gene 1(IEG1) transcription, as well as through downregulating the extracellular-signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling pathway. The alleviation of viral infection was also shown to link with immunomodulatory effects of garlic and its OSCs. Clinical studies further demonstrated a prophylactic effect of garlic in the prevention of widespread viral infections in humans through enhancing the immune response. This review highlights that garlic possesses significant antiviral activity and can be used prophylactically in the prevention of viral infections.

Keywords: AGE, Aged garlic extract; AIV-H9N2, Avian influenza virus-H9N2; ALT, Alanine aminotransferase; ARVI, Acute respiratory viral infection; AdV-3, Adenovirus-3; AdV-41, Adenovirus-41; Allium sativum; CBV-3, Coxsackie B −3; CPE, Cytopathic effect; CoV, Coronavirus; DADS, Diallyl disulfide; DAS, Diallyl sulfide; DATS, Diallyl trisulfide; DDB, Dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate; ECHO11, Echovirus-11; ECM, Extracellular matrix; ERK, Extracellular-signal-regulated kinase; FDA, Food and drug administration; Functional food; GE, Garlic extract; GLRaV‐2, Grapevine leafroll‐associated virus 2; GO, Garlic oil; GRAS, Generally regarded as safe; HAV, Hepatitis A virus; HCMV, Human cytomegalovirus; HIV-1, Human immunodeficiency virus-1; HPV, Influenza B virus Human papillomavirus; HRV-2, Human rhinovirus type 2; HSV-1, Herpes simplex virus-1; HSV-2, Herpes simplex virus-2; Hp, Haptoglobin; IAV-H1N1, IBV Influenza A virus-H1N1; IEG1, Immediate-early gene 1; IEGs, Immediate-early genes; Immunomodulatory; LGE, Lipid garlic extract; MAPK, Mitogen activated protein kinase; MARS-CoV, Middle East respiratory syndrome coronavirus; MDCK cells, Madin-darby canine kidney cells; MeV, Measles virus; NA, Not available; NDV, Newcastle disease virus; NK, Natural killer; OSCs, Organosulfur compounds; Organosulfur compounds; PGE, Powdered garlic extract; PIV- 3, Parainfluenza virus-3; PRRSV, Porcine reproductive and respiratory syndrome virus; PRV, Porcine Rotavirus; PVY, Potato Virus Y; Pandemic; RCTs, Randomized clinical trials; RMCW, Recalcitrant multiple common warts; RV-SA-11, Rotavirus SA-11; SAC, Serum antioxidant concentration; SAMC, S-allyl-mercaptocysteine; SAMG, S-allyl-mercapto-glutathione; SARS-CoV, Severe acute respiratory syndrome coronavirus; SI, Selectivity index; SRGE, Sustained release garlic extract; SWV, Spotted wilt virus; VSV, Vesicular stomatitis virus; VV, Vaccinia virus.

Fig. 1

Organosulfur compounds of garlic: (A) Structure of OSCs identified in garlic; (B) Biosynthesis of allicin from alliin; (C) Transformation of allicin to its derivatives at different condition; (D) Extraction of major sulfur constituents (other OSCs also yielded as minor amount) from garlic with different solvent systems.

Fig. 2

Proposed antiviral mechanism of action of garlic extract and its OSCs (GE/OSCs) in different viral life cycle. Fig. 2(A) shows the essential steps in the life cycle of “+ssRNA viruses” such as HIV-1. In this figure, GE/OSCs have shown to inhibit the entry of the virus into the host cells, inhibit the viral reverse-transcription steps i.e. block the conversion of viral RNA genome into a DNA duplex, as well as inhibition of viral integration steps. Therefore, ultimately block the viral replication and reduced cellular viral load. Fig. 2(B) shows the essential steps in the life cycle of “DNA viruses” such as HCMV or herpes virus. In this figure, GE/OSCs have shown to inhibit the entry of the virus and fusion of its genetic materials into the host cells as well as inhibit viral replication and transcription steps to block the viral replication and reduced cellular viral load. Whereas, Fig. 2(C) shows the essential steps of “-ssRNA viruses” cycle such as influenza virus. In this figure, GE/OSCs have shown to inhibit the entry and uncoating of its genetic materials into the host cells, inhibit the conversion of (−) viral RNA to (+) viral RNA steps and during the replication steps as well as assembly and release of new virions steps of their life cycle and ultimately reduced the viral load in the infected cells.

Fig. 3

Proposed mechanism of immunomodulatory effect of garlic and its OSCs in viral infected host. In the figure, the mechanism of immunomodulatory activity of garlic and its OSCs shown to involve in the elevation of innate immune response via macrophage and natural killer (NK) cells as well as enhancing adaptive immunity through T cells and B cells.