Antiviral properties of placental growth factors: A novel therapeutic approach for COVID-19 treatment

Abstract

The current challenge of the COVID-19 pandemic is complicated by the limited therapeutic options against the virus, with many being anecdotal or still undergoing confirmatory trials, underlining the urgent need for novel strategies targeting the virus. The pulmotropic virus causes loss of oxygenation in severe cases with acute respiratory distress syndrome (ARDS) and need for mechanical ventilation. This work seeks to introduce placental extract-derived biologically active components as a therapeutic option and highlights their mechanism of action relevant to COVID-19 virus. Human placenta has been used in clinical practice for over a century and there is substantial experience in clinical applications of placental extract for different indications. Aqueous extract of human placentacontains growth factors, cytokines/chemokines, natural metabolic and other compounds, anti-oxidants, amino acids, vitamins, trace elements and biomolecules, which individually or in combination show accelerated cellular metabolism, immunomodulatory and anti-inflammatory effects, cellular proliferation and stimulation of tissue regeneration processes. Placental extract treatment is proposed as a suitable therapeutic approach consideringthe above properties which could protect against initial viral entry and acute inflammation of alveolar epithelial cells, reconstitute pulmonary microenvironment and regenerate the lung. We reviewed useful therapeutic information of placental biomolecules in relation to COVID-19 treatment. We propose the new approach of using placental growth factors, chemokines and cytokine which will execute antiviral activity in coordination with innate and humoral immunity and improve patient's immunological responses to COVID-19. Executing a clinical trial using placental extract as preventive, protective and/or therapeutic approach for COVID-19treatment could advance the development of a most promising therapeutic candidate that can join the armamentaria against the COVID-19 virus.

Being pregnant in the COVID‐19 pandemic: Effects on the placenta in all aspects

“…Especially IFNs play an important role in the protection process; additionally, it has shown that placental trophoblast-derived IFNs and TNF-α responsible to impair virus replication and activity. 40,43 Production of IFN-1 control infection systemically and IFN-3 control it locally at the barrier surface of the placenta. Additionally, Hofbauer cells (placental macrophages) show intrinsic antiviral activity in the placenta.…”

“…Growth factors (GFs), such as hepatocyte‐nerve‐epidermal‐fibroblast‐insulin‐like colony‐stimulating vascular endothelial GFs; cytokines or chemokines like IL‐1,2,3,4,6,8,10 and IFN (interferon)‐γ, TNF‐α, TGF (transforming growth factor)‐β; metabolic compounds such as nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide phosphate hydrogen (NADPH), nitric oxide (NO); antioxidants like superoxide dismutase (SOD), catalase, glutathione peroxidase; amino acids, such as alanine, arginine, histidine, tyrosine; vitamins and trace elements like zinc, copper, iron, selenium, manganese; and other components, such as collagen, elastin, carotenes, can be summarized as biologically active components in the placenta 40 . Each component has important roles in different functions; also it would be more appropriate to study more closely the antiviral activity of placenta extracts for COVID‐19.…”

“…The placenta shows a protective property due to GFs, chemokines, and cytokines that are described above so that viruses do not infect the fetus from the mother's circulation. Especially IFNs play an important role in the protection process; additionally, it has shown that placental trophoblast‐derived IFNs and TNF‐α responsible to impair virus replication and activity 40,43 . Production of IFN‐1 control infection systemically and IFN‐3 control it locally at the barrier surface of the placenta.…”

“…In addition to IFNs, GFs within EVTs, CTBs, and STBs form the barrier for the viruses between mother and fetus from the 6th month of gestation. Because of this important property of placental GFs, if they use as antiviral drugs, the third trimester is suitable for the isolation because GFs peak during the third trimester 40 . Taken together, after the isolation process, the use of placental GFs, cytokines, and chemokines as an agent to improve the patient's immunological responses to COVID‐19 may be new hope in the treatment process.…”

“…Because of these rich content, the placenta shows antiviral, anti‐inflammatory, antibacterial, immunoregulatory activities, and also plays a critical role in therapeutic efficacy on wound healing, tissue regeneration, cellular proliferation, osteoarthritis, antiaging, chronic pain, brain or liver damage, and so forth. Because of these properties, placenta extracts have been considered “biological drugs” for over centuries and have been used in experimental and clinical trials 40–42 …”