Povidone Iodine (PVP-I) mouth gargle/nasal spray may be the simplest and cost effective therapeutic antidote for COVID-19 Frontier

Need an effective protocol for health workers against dangerous and unpredictable SARS CoV-2, a RNA lipid bi-layer enveloped beta-coronaviruses which contains Hemagglutinin Esterase (HE) protein binds with human gene through Angiotensin-Converting-Enzyme 2 (ACE2) and CD147 receptor. Povidone-iodine (PVP-I) has effective virucidal activity by those receptors inhibition and direct kill the virus by membrane disruption. PVP-I gargle, nasal spray and eye drop in case of accidental exposure is well tolerated easy use and has 2-3 hours contamination protection properties. So, uses gargle and nasal spray every 3 hours during shifting duty of health care provider which will cover the total protection and reduced social contamination. Mini Review Povidone Iodine (PVP-I) mouth gargle/nasal spray may be the simplest and cost effective therapeutic antidote for COVID-19 Frontier Ibrahim Khalil1 and Parometa Barma2* 1BDS, MS, PhD Fellow, Professor and Head of Department Conservative Dentistry, City Dental College and Hospital, Dhaka-1219, Bangladesh 2BDS, MPH, M. Phil Fellow, Medical Offi cer, TMSS Medical College and Hospital, Bogura, Bangladesh Received: 25 June, 2020 Accepted: 20 July, 2020 Published: 21 July, 2020 *Corresponding author: Dr. Parometa Barma, BDS, MPH, M. Phil Fellow, Medical Offi cer, TMSS Medical College and Hospital, Bogura, Bangladesh, Tel: +88001745531976; E-mail:


Introduction
Povidone Iodine is Polymer Polyvinylpyrrolidone (PVP-I) well tolerated then other conventional antiseptic agent and completely soluble in cold and mild warm water has pharmacological role of strong anti-viral effect against SARS-CoV, MERS-CoV and recent SARS-CoV-2 [1,2]. SARSCoV-2 occupies host cells through two receptors: angiotensinconverting enzyme 2 (ACE2) and CD147 (also known as Basigin or EMMPRIN). CD147 is a transmembrane protein and highly glycosylated of the immunoglobulin super family which acts as the main upstream stimulator of Matrix Metalloproteinases (MMPs). Virus spike protein (SP) fi xes to ACE2 or CD147 on the host cell, mediating viral invasion and spreading to other cells [3,4]. Like RBCs and type II alveolar cells (AT2) of lung, this CD147 also present in tear and ocular tissues, like conjunctiva, corneal epithelium, endothelium, keratocytes, and retinal pigment epithelium but ACE 2 receptor absent in such healthy ocular tissues [5]. So, some shorts of upper respiratory tract infection due to binding of SARS CoV-2 with CD147 in ocular tissues then drain into nasal cavity via nasolacrimal duct [3,4]. Study demonstrate virus found in tear/conjunctival specimen is 1.949% of total COVID19 patients. These outcomes point out a possibility of local replication of the virus followed by systemic involvement, especially in cases of droplet or aerosol transmission through the ocular route [6,7]. Another recent study in China almost 31.6% of patients with COVID-19 had ocular involvement. It was also interesting to note that 91.7% of the patients with COVID-19-related conjunctivitis tested positive on a nasopharyngeal swab [8].
In case of SARS-CoV-2, initial interactions between its host receptor (either ACE2 or CD147) and the spike protein S1 domain are the initiating event in establishment of human host infection [9,10]. The inhibitory effect of PVP-I on Hemaggulitinin(HA) protein mediated ACE2 and receptor binding host cell transmission decline the cross infection from patients to health care workers also true in opposite order [1,11,12]. The lipid bi-layer envelop The beta-coronaviruses contain several Hemagglutinin Esterase (HE) protein as fi fth structural protein [13,14]. Abundant ACE2 receptor is identifi ed in oral tissues, especially in epithelial cells of tongue, type II alveolar cells (AT2) of lung, esophagus upper, stratifi ed epithelial cells, heart, lungs, kidneys, and gastrointestinal tract, thus facilitating viral entry into target cells [12,15]. High amount of ACE2 receptor is in lymphocytes of oral cavity [12], salivary glands which is an early target for SARS-CoV-2 [16]. Prophylactic mouth rinse/ gargle and nasal spray inactivate the heamaggulitin esterase activity as well as enhance absorption of ACE2 as receptor of host cell infection [17,18].
The process of SARS CoV-2 entering into the host cell begins through the attachment of the S glycoprotein to the ACE2 and CD147 receptor of host cells (such as in type II pneumocytes in the lungs) [19]. Topical povidone iodine along with dexamethasone was found to be very effective in rabbit adenoviral conjunctivitis [21]. In clinical settings, PVP-I (1% and 5%) already showed clinical benefi t in cases of adenoviral conjunctivitis. 1% topical PVP-I (eye drop) on stat dose has prophylactic or preventive role of during accidental ocular exposure to SARS CoV-2 [22,23].
Few well-designed studies have established the effi cacy of PVP-I eye drops in viral conjunctivitis [21]. For a case of conjunctivitis with COVID-19, this preparation may help to reduce the viral load due to its action against a wide range of viruses. Burning and irritation is a signifi cant side effect of the drug, which can be effectively reduced by diluting 1 mL of 5% PVP-I with 4 mL of BAK containing lubricant drops. This formulation will not only ensure patient comfort but also it will have the advantage of dual antiviral action with BAK and PVP-I  Below 0.5% PVP-I gargle once or twice a day up to sixmonths showed no alteration in thyroid hormone levels (serum T3/T4 and free T4) but small increase in TSH levels within normal range [31]. In case of pediatric patient below 6 years not recommended, 6years or above may use single episode of PVP-I if mandatory [1,32].

Recommendation
According to evaluation of study we found, use of 0. Person who staying or related to COVID-19 patient including asymptomatic COVID-19 patients or has transmission risk, all should continue the PVP-I gargle and nasal spray in every 3 hour or 4 times a day. There is evidence of 0.4% to 0.23% has no side effect even continuous use of 3 month to 2 years [15,33,[34][35][36][37][38][39]. More over, gag refl ex and unconscious cases may be recommended 0.4%-0.5% throat spray.