Can Tenofovir diphosphate be a candidate drug for Sars-Cov2?
First clinical perspective
Dear editor,
COVID-19 pandemic continues to spread across the world in late September
2020. To date, total cases of COVID-19 exceed 33 million including
996.342 deaths according to the WHO data. Governments still taking
numerous measures to prevent the spread of the Severe Acute Respiratory
Syndrome Coronavirus 2 (SARS-CoV-2).1 The estimate for
the basic reproduction number during the early stages of the COVID-19
outbreak is recently reported as 4.22 ± 1.69 in Europe that shows
COVID-19 has a high transmission rate. In addition, the median
incubation period is reported as 6 (minimum 2, maximum 14)
days.2 Although hydroxychloroquine, oseltamivir,
remdesivir, favipiravir have been reported as an anti-SARS-CoV-2 effect,
it is still unclear the fully effective protective drug and
treatment.3
A 31-year-old man who has a high fever, chills, loss of smell, and the
sore threat presented to the pandemic hospital. He had close contact
history with COVID-19 patients in his workplace 6 days ago. The patient
was diagnosed as COVID-19 based on the real-time
reverse-transcriptase-polymerase chain reaction (RT-PCR) in
nasopharyngeal swabs. He had been taken in home-quarantine and started
orally 2x200 mg hydroxychloroquine. Although he had close contact with
his wife without measure in the home his wife did not show any symptoms
and signs of COVID-19. 18 days after the first symptoms, the antibody
test was performed to the patient and his wife and her PCR test along
with antibody test negative. The patient had IgG positivity while his
wife did not develop antibody positivity including both IgM and IgG
(Figure 1). She had been receiving Tenofovir 245 mg daily for two years
for chronic hepatitis B. She did not have any other disease as well as
drug history.
SARS-CoV-2 is a positive-sense single-strand RNA virus that has
RNA-dependent RNA polymerase property.4 RNA-dependent
RNA polymerase is one of the main target points for the treatment of RNA
viruses. Nucleotide analogs act as substrates and inhibit viral
polymerases. Tenofovir diphosphate which is a nucleoside analog
reverse-transcriptase inhibitor is an active form of Tenofovir
alafenamide that is used for hepatitis B and
HIV/AIDS.5 Recently, it has been shown that nucleoside
analogs including 3’-fluoro-3’-deoxythymidine triphosphate,
3’-azido-3’deoxythymidine triphosphate and Tenofovir diphosphate are
able to terminate polymerase extension of coronavirus by consolidated
with SARS-CoV-2 RNA-dependent RNA polymerase.6 Given
the high reproduction number of SARS-CoV-2 and long-term close contact
of the case, it can be speculated that Tenofovir could interfere with
the transmission of COVID-19. In accordance with the previous in vitro
study, our case is the first clinical report that supports the possible
clinical protective effect of Tenofovir. Further randomized clinical
studies will illuminate whether Tenofovir may be used as an effective
new drug for COVID-19.