key: cord-0922460-wxl2pim4
authors: Nawaz, Muhammad; Ali, Muhammad Asad; Ashraf, Muhammad Adnan; Shabbir, Muhammad Zubair; Shabbir, Muhammad Abu Bakr; Altaf, Imran; Raza, Sohail; Rafique, Saira; Hassan, Sohail; Sardar, Nageen; Mehmood, Adnan; Aziz, Muhammad Waqar; Fazal, Sehar; Khan, Muhammad Tahir; Attique, Muhammad Moavia; Asif, Ali; Ullah, Zia; Iqbal, Mubashir; Imtiaz, Talha; Anwar, Muhammad; Mukhtar, Nadia; Yaqub, Tahir
title: An assessment of efficacy of Iodine complex (Renessans) against SARS-CoV-2 in non-human primates (Rhesus macaque)
date: 2020-11-18
journal: bioRxiv
DOI: 10.1101/2020.11.17.377432
sha: 9923bd79e7978eda959550592ff17521f7bee2ac
doc_id: 922460
cord_uid: wxl2pim4

Renessans is an iodine complex which has proven in vitro antiviral activity including Anti-SARS-CoV-2 activity. The present study was designed to determine its efficacy against SARS-CoV-2 in monkeys (Rhesus macaque). A total of 14 monkeys were divided into four groups: A) Prophylactic group (n=03), (B) Treatment group (n=03), (C) infection control group (n=04) and (D) negative control group (n=04) and were housed in BSL-3 Animal facility while group D was housed at another animal house. Group A was administered with Renessans @ 2.85 mg/7 kg from 5 days prior to the infection to 08 days post infections (DPI). Group B was administered with Renessans from 03-08 DPI @ 2.85 mg/7 kg. Group C was administered with WIF only. The infection @ 2 × 106 TCID of SARS-CoV-2 was given to all group monkeys through intranasal and oral route under anesthesia. Nasal swab samples (at different times) and fecal matter on daily basis were collected for the detection of SARS-CoV-2 through real-time quantitative PCR. Three monkeys (one from each of group A, B and C) were euthanized at 07 DPI to determine the gross pathological lesions and SARS-CoV-2 detection from internal tissues. Nasal swabs from all the monkeys from group A, B and C were positive for SARS-CoV-2 at 02 and 07 DPI (Day 05 of treatment). At 14 DPI, all (100%) nasal swabs from group A were negative for SARS-CoV-2 while 50% and 100% were positive from group B and C, respectively. At 21 DPI, monkeys from group B were negative and all in group C were still positive for SARS-CoV-2. Similarly, fecal matter of monkeys in group A and B was returned negative in significantly lesser time as compared to monkeys from infection control group. Based on these research findings it is concluded that the Renessans has in-vivo SARS-CoV-2 activity and may result in early clearance of SARS-CoV-2. Therefore, a clinical trial of the drug in COVID-19 patients may reveal its anti-COVID-19 potential.

Introduction: 57 Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) was first time 58 reported as the etiologic agent of coronavirus disease 2019 in December 2019 at 59 a wholesale seafood market in Wuhan, Hubei province, China (Lake, 2020; WHO, 2020). 60 According to the World Health Organization (WHO) that more than 5.3 million confirmed 61 cases and around 340,000 fatalities have been reported all over the world since its first report 62 (WHO, 2020). Noteworthy, therapeutic options for SARS-CoV-2 have not been developed so far and hence 86 only supportive therapy is provided to the patients (Raza et al., 2020) . Therefore, present study 87 was designed to develop a treatment for SARS-CoV-2. This study was based on our previous 88 in vitro study (under review) findings in which Renessans (antiviral drug) showed promising 89 results. In current study, we determine its in vivo efficacy against SARS-CoV-2 in monkeys 90 (Rhesus macaque). A total of 14 monkeys were divided into 4 groups and SARS-CoV-2 91 infection was given to group A, B and C. Pre and post infection nasal as well as fecal sampling 92 was performed for the detection of SARS-CoV-2 by real-time quantitative PCR. Furthermore, 93 one monkey from each group A, B and C were euthanized for determining the gross 94 pathological lesions as well as SARS-CoV-2 from different tissues samples. Present study 95 findings did reveal that Renessans have antiviral activity and helps in early clearance of SARS-96 CoV-2. We believe that current study findings will provide a baseline for clinical trial against The antiviral drug (Renessans) was administered @ 2.85 mg/7 kg at the date 22 August 2020 114 to group A from 5 days prior to the infection to 08 days post infection (DPI). Group B was 115 administered with Renessans after the onset of clinical signs and symptoms from 03-08 DPI @ 116 2.85 mg/7 kg. Group C was administered with WIF only. SARS-CoV-2 (GenBank accession 117 number MW031802) infection @ 2 x 10 6 TCID was given to group A, B and C through 118 intranasal and oral route under anesthesia (mixture of ketamine and xylaz) at the date 26 August 119 2020. Additionally, body temperature of group A, B and C monkeys was also monitored on 120 daily basis throughout the experiment after the onset of clinical signs and symptoms.

Fecal and Nasal swab Sampling: 122 Fecal and nasal swab sampling was performed to determine the shedding of SARS-CoV-2 123 through these routes. All monkeys of group A, B and C were anesthetized for nasal sampling. 124 We did nasal sampling five times during the whole experiment; firstly one day before the 125 infection and then at 2 DPI, 7 DPI, 14 DPI and 21 DPI from all monkeys of group A, B and C. 126 However, we started fecal sampling on daily basis from day 0 (infection date 26-08-2020) to 127 16-09-2020 (experiment ending date). For better understanding, experimental plan or design is 128 given in Figure 1 . (Table 1 ). These findings suggesting that antiviral drug (Renessans) did have in-vivo SARS- Table 2 . In the light of current study findings, it is concluded that the Renessans has an in-vivo SARS-

CoV-2 activity and may result in early clearance of SARS-CoV-2. Therefore, we believe that 215 current study may provide a basis for clinical trial of the drug in SARS-CoV-2 patients and 216 reveal its anti-SARS-CoV-2 potential. 

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